Purpose
To lay down a procedure for the preparation of the
validation master plan which summarizes the company’s overall philosophy,
intention and strategy of execution of the validation program in the
organization.
Procedure:
Introduction to Validation
Master Plan
Validation is defined as “Confirmation, through the
provision of objective evidence that the requirements for a specific intended
use or application have been fulfilled.
A Validation Master Plan is a document that summarizes
the firm’s overall philosophy, intentions and approach to be used for
establishing performance adequacy.
The validation plan is a strategic document that should
state what is to be done, the scope of approach, the schedule of validation
activities and tasks to be formed.
The plan should also state who is responsible for
performing each validation activity. The plan should be reviewed and approved
by designated management.
The VMP should present and overview of the entire
validation operation, its organizational structure, its content and planning.
The core of the VMP being the list/ inventory of the items to be validated and
the planning schedule.
Principle
Validation in general requires a meticulous preparation
and careful planning of
the various steps in the process. In addition, all work
involved should be carried
out in a structured way according to formally authorized
standardized working
and administrative procedures. In addition, validation
is characterized by:
Multidisciplinary approach: A specific
characteristic of validation work is that it requires the collaboration of
experts of various disciplines such as pharmacists, technologists,
metrologists, chemical analysts, microbiologists, engineers, experts on Q.A.
validation etc.
Time constraints: Generally,
validation work is submitted to rigorous time schedules. These studies are
always the last stage prior to taking new processes, facilities into routine
operation.
Costs: Validation studies are costly as they require
time of highly specialized personnel and expensive technology.
Purpose:
- The VMP should present an overview of the entire validation operation, its organizational structure, its content and planning. The core of the VMP being the list / inventory of the items to be validated and the planning schedule.
- A VMP helps Management:
- To know what the validation programme involves with respect to time, people and money.
- To Understand the necessity for the programme;
- A VMP helps all members of the validation team:
- To know their tasks and responsibilities.
- A VMP helps GMP inspectors:
- To understand the firm's approach to validation and the set up an organization of all validation activities.
Scope:
All validation activities relating to critical
technical operations, relevant to product and process controls within the
organization shall be included in VMP.
This includes qualification of critical manufacturing
and control equipment.
It should comprise all Prospective, Concurrent,
Retrospective Validations as well as Re-validations (as applicable) of large
project like the construction of a new facility, often the best approach is to
create a separate VMP (In such situation the VMP should be part of the total
project management).
Definitions: The definitions
given below apply to the terms used in this SOP. They may have different
meanings in other contexts.
Calibration: The performance
of tests and retests to ensure that measuring equipment (e.g. for temperature,
weight, pH) used in a manufacturing process or analytical procedure (in
production or quality control) gives measurements that are correct within
established limits.
Change Control: A written procedure
that describes the action to be taken if a change is proposed (a) to
facilities, materials equipment, and / or processes used in the fabrication,
packing, and testing of drugs, or (b) that may affect the operation of the
quality or support system.
Critical Process parameter: A
parameter which if not controlled will contribute to the variability of the end
product.
Cleaning Validation: Documented
evidence to ensure that cleaning procedures are removing residues to
predetermined levels of acceptability, taking into consideration i.e. batch
size dosing toxicology, equipment size etc.
Qualification: Qualification is
the planning, carrying out and recording of tests on equipment and systems which
form part of the validated process, to demonstrate that it will perform as
intended.
Design Qualification (DQ):
Documented evidence that the premises, supporting utilities, equipment and
processes have been designed in accordance with the requirements of GMP.
Installation qualification
(IQ): IQ is the documentary evidence to verify that the equipment has
been built and installed in compliance with design specifications.
Operational qualification
(OQ): OQ is the documentary evidence to verify that the equipment
operators in accordance with its design specifications in its normal operating
range and performs as intended throughout all anticipated operating ranges.
Performance Qualification
(PQ): PQ is the documentary evidence which verifies that the equipment
or system operates consistently and gives reproducibility within defined
specifications and parameters for prolonged periods. (the term “Process
Validation” may also use).
Process Re-validation:
Required when there is a change in any of the critical process parameters,
formulation, primary packaging components, raw material fabricators, major
equipment or premises. Failure to meet product and process specifications in
sequential batches would also require process revalidation.
Major Equipment’s: A piece of equipment’s
which performs significant processing steps in the sequences of operations
required for fabrication/packaging of drug products. Some examples of major equipment’s
include manufacturing and storage vessels, filling machines, BOV filling
machine, leak test water bath etc.
Validation:
Documented series of actions that prove that any procedure, process
equipment, material, activity or system performs its intended functions
adequately and consistently, and lead to the expected results of uniform batches
that meet the required specifications and quality attributes.
Process Validation: Documented
evidence, which provides a high degree of assurance that a specific process
will consistently produce a product meeting its pre-determined specifications
and quality characteristics.
Prospective Validation:
Validation carried out during the development stage by means of a risk analysis
of the production process, which is broken down into individual steps; these
ate then evaluated on the basis of past experience to determine whether they
may lead to critical situations.
Concurrent Validation: Validation
carried out during routine production of product intended for sale.
Retrospective Validation:
Involves the examination of past experience of production on the assumption
that composition, procedures and equipment remain unchanged.
Re-validation: Involves the repeat of the initial
process validation to provide assurance that changes in the process and / or in
the process environment, whether intentional or unintentional, do not adversely
affect process characteristics and product quality.
Validation protocol (VP): A
written plan of actions stating how process validation will be conducted; it
will specify who will conduct the various tasks and define testing parameters;
sampling plans, testing methods and specification; will specify product
characteristics, and equipment to be used. It must specify the minimum number
of batches to be used for validation studies it must specify the acceptance
criteria and who will sign/ approve/ disapprove the conclusions derived from
such a scientific study.
Validation Report (VR): The VR
is a written report on the validation activities, the validation data and the
conclusions drawn.
Validation Master Plan (VMP):
VMP is high level document that establishes as umbrella validation plan for the
entire project and summarizes the manufacturer’s overall philosophy and
approach to be used for establishing performance adequacy. It provides
information on the manufacturer’s validation work performance and defines
details of and time-scales for the validation work to be performed, including
stating the responsibilities relating to the plan.
Validation Team: A multi-disciplinary
team of personnel primarily responsible for conducting and/or supervising
validation studies. Such studies may be conducted by person(S) Qualified by
training and experience in a relevant discipline.
Worst Case: A condition or set of
conditions encompassing upper and lower processing limits and circumstances,
within SOP’s which pose the greatest chance of product or process failure when
compared to ideal conditions. Such conditions do not necessarily include
product or process failure.
Validation Policy:
- Validation is an essential and integral part of Good Manufacturing Practice (GMP).
- It is, therefore, an element of the quality assurance programme associated with a particular product or process. It is accepted that the basic principles of quality assurance have as their goal the production of products that are fit for their intended use. These principles may be stated as:
- Quality, safety and efficacy must be designed and built into the product.
- Quality cannot be inspected or tested into the finished product.
- Each step of the manufacturing process must be controlled to maximize the probability that the finished product meets all quality and design specification.
- Validation of processes and system is fundamental to achieving these goals.
- It is by design and validation of both process and process controls that a manufacturer can establish confidence that all manufactured product form successive lots will be acceptable.
- All equipment’s, stages of process, cleaning method, facility & utilities which have direct impact on product identity, quality, purity, safety and efficacy shall be validated.
- Organization shall provide necessary resources for organizing and executing the validation activities.
- Chance controls, re-validation, re-qualification and calibration measures shall be established and implemented to identify, document and review changes to all variables that could alter the validated status of each manufacturing process, equipment or system.
- Responsibilities
Brief Description of Facility and plant
Brief information describing the overall organization
followed by brief information about the site covering the regulatory credential
available & activities performed at site.
These shall include but not limited
Warehouse
Manufacturing and Packing area
Quality Control
Quality Assurance
Utilities
Qualification / Validation concept:
There are different stages in the performance of
qualification. These include:
User requirement specification (URS):
The basic purpose for preparation of the URS shall be
to provide the appropriate design and performance requirements for procurement
of equipment/ instrument/system including major add-on component or major
modification / expansion of the area so as to meet the in-house requirement as
well as compliance with current Good Manufacturing Practices.
Design Qualification (DQ):
Design qualification (DQ) constitutes the assurance
that the premises, supporting utilities, equipment and processes have been
designed in accordance with the requirements of GMP.
Factory Acceptance Test (FAT):
Factory acceptance test (FAT) shall be performed at the
supplier’s end and before dispatch designed as per the requirements specified
in the URS, the equipment operates as intended and meets the requirement of
cGMP.
Site Acceptance Test (SAT):
Site acceptance test (SAT) shall performed at site
after receiving, equipment/instrument/system designed as per the requirements
specified in the URS and meets the requirement of cGMP.
Installation Qualification (IQ):
- Installation Qualification (IQ) is associated with the performance of tests to ensure that the installation of machine, measuring devices, utilities and manufacturing areas used in the manufacturing processes are:
- Appropriately selected;
- Correctly installed; and
- Will be operating in accordance with the established specifications.
- An IQ protocol should be used to document the specific (static) attributes of a facility or item of equipment, in order to prove that the installation of the unit has been correctly performed and that the installation specifications of the manufacturer have been met.
- The IQ protocol should be numbered, dated and approved for issued by appropriately authorized personnel. The IQ protocol should contain at least a procedure number, purpose of the facility or equipment, design and construction details, details of services required and provided, addenda such as chart recorder traces, technical drawings, and acceptance criteria.
- The protocol should be written for all critical processing equipment and system used within a manufacturing/ packing testing facility. It should list all the identification information, location, utility requirements and safety features of the equipment.
- During the IQ process it should be verified that the item matches the purchase specification and that all the drawings, manuals, spare parts list, vendor address and contract number, and other important documentation are available.
- Operational Qualification (OQ) is associated with the performance of the equipment to ensure that the functions of machine, measuring devices, utilities and manufacturing areas operate according to its operational specification in the selected environment.
- An OQ protocol is used to document specific (dynamic) attributes of a facility or item of equipment to prove that it operates as expected throughout its operating range.
- As with the IQ protocol, the OQ protocol should be numbered, dated and formally approved. Tests should be designed to demonstrate that the unit performs properly at the limit of its operating conditions, as well as within its normal operating range. Measurements made on a statistical basis should be fully described in the protocol.
- The OQ protocol should outline the information required to provide evidence that all the components of the system or equipment operate as specified. It should include verification of all the operation controls alarm points switches and displays. The protocol should reflect all SOPs for operation, maintenance and calibration, and training of operations.
- The OQ protocol should include an introduction and objective, identification information, visual inspection parameters, functioning of switches and indicator lights, check and calibration of sensors, probes gauges, recorders air flow rates, direction, pressures, temperatures, filter integrity and efficiency tests, cleaning procedures, details of qualification instrumentation used acceptance criteria, actions resulting from the OQ () what to do when out of specification results are obtained) re-qualification time scales and triggering factors.
- The OQ data should be formally reviewed and approved before process validation can commence.
- Performance Qualification (PQ) is done after both IQ and OQ have been completed, reviewed and approved.
- The PQ protocol describes the procedure to be followed for demonstrating that a system or equipment can consistently perform and meet required specification under routine operation (or worst case conditions).
- The PQ protocol may be used in cases where performance date is gathered over a long period of time. Under these circumstances, it may be difficult to “sign off” the operational qualification (OQ) as complete. One solution is to define and approve to OQ at a single point in time, and create a PQ protocol, which is then used as the vehicle for amassing the ongoing data.
Equipment should be subject to re-qualification in
accordance with a defined schedule.
Re- qualification is subdivided into periodic
re-qualification and re-qualification after change. These changes include
adaptation of equipment, maintenance movement and repairs.
General Acceptance Criteria:
The equipment / instruments qualified shall meet the
predetermined criteria as defined in the respective protocol / report.
Validation approach
- There are two basic approaches to validation – the experimental approach and an approach based on the analysis of historical data.
- The experimental approach, which is applicable to both prospective and concurrent validation, may involve.
- Extensive product testing, which may involve extensive sample testing, with the estimation of confidence limits for individual result and batch homogeneity.
- Simulation process trials, which involve mainly aseptic sterilization with the target contamination level of microbial growth not exceeding 0.1%.
- Challenge/worst case tests, which determine the robustness of the process.
- Controls of process parameters being monitored during normal production runs to obtain additional information on the reliability of the process.
- The approach based on the analysis of historical data, which is applicable to retrospective validation combines all available historical data of a number of batches with the outcome of the results, indicating whether the process is under control. No experiments are performed.
Type of Validation
Process Validation: Type of process
validation include:
Prospective Validation:
- Prospective Validation is carried out during the development stage of product. If the validation programme is designed and the protocol issued before the equipment or facility comes on stream, or before the product manufactured by the process being validated is distributed, then it constitutes prospective validation. It should be performed by means of a risk analysis of the production process, which is broken down into individual steps. It should involve the establishment of documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do, based on a pre-planned validation protocol.
- Prospective validation is required for new manufacturing formulae or methods of preparation where the latter are adopted. Steps should be taken to demonstrate their suitability for routine processing.
- The purpose is to ensure that the defined process, using the materials and equipment specified, should be shown to yield a product that is consistently of the required quality.
- In general, the final batch size should not be more than 10 times the batch size of the representative development batches.
- The process should include the identification and evaluation of individual steps, the identification of critical situations, design of trial plans and set of priorities, performance of trials and recording of results, and finally assessment and evaluation or result. If the results are unsatisfactory then the processes are modified and improved until acceptable results are obtained. This is essential to limit the risk and errors that may occur on production scale.
- Concurrent validation is carried out during normal production. This method of validation can only be successful if the development stage has resulted in proper understanding of the fundamentals of the process. It is carried out during normal production of products intended for sale. It should involve closed and intensive monitoring of the steps and critical points in at least the first three production scale batches. The results of in-process controls can be used to provide some of the evidence required for validation but these are no substitute for validation.
- Validation in the production unit mainly comprises of the determination and evaluation of the process parameters of the facilities applied for the scale-up to final batch size. The control of all critical process parameters, the results of the in-process controls, final controls and stability tests should prove the suitability of the important individual steps of a procedure.
- Retrospective validation is based on are view of historical manufacturing and testing data, and is the analysis of accumulated results from past production to assess the consistency of a process.
- It is assumed that the composition, procedure and equipment remained unchanged.
- During retrospective validation results of in-process and final control tests are evaluated.
- It should include trend analysis of test results and a close examination of all recorded process deviations. Quality control charts could be used when performing retrospective validation. A total of 10-20 batches (or more), manufactured over a period of 12 months, should be used when reviewing the results, to provide a statistically significant picture. Trend analysis should be conducted.
- Rejected batches should not be included in at the analysis. Failure investigations should however, be performed separately.
- As retrospective validation is not considered to be a quality assurance measure it should not be applied to new processes or products, It is not the preferred method of validation and should be used in exceptional cases only.
- When the results of retrospective validation are positive it is considered to be an indication that the process is not in need of immediate attention, and any be validated later in accordance with the normal schedule.
- Steps during retrospective validation include:
- Choosing a critical quality parameter (e.g. assay value;
- Extracting the analytical results from each batch (the results of a batch are grouped a subgroups);
- Calculating the grand average (process average) and control limit and plotting the results on graphs or charts.
- The process may be considered reliable if the plotted data are within the control limit and the variable of individual results is stable (or trends to decrease). Where the existing data are inadequate additional tests should be performed.
- Acceptance criteria must be set before validation, and not after the experiment a phase of the work has been completed. This is another reason why retrospective validation is not encouraged since the acceptance criteria are set after all the analytical work has already been performed.
- Cleaning, like any other critical process, should be validated. The objective of cleaning validation is to prove that the equipment is consistently cleaned from product, detergent and microbial residues to and acceptable level, to prevent contamination and cross-contamination.
- There should be written SOPs detailing the cleaning process for equipment and apparatus.
- The SOP for cleaning a piece of equipment should only be written once the cleaning process has been validated. The validated procedure should thus be followed consistently, adhered to appropriately document and recorded in cleaning logs and maintained to ensure the equipment is always cleaned as required.
- Before the cleaning procedure is validated a written SOP should be available, detailing how the cleaning processes will be validated and referring to accountabilities, acceptance criteria microbiological aspects (bio-burden control) and re-validation requirements. The complexity and design of the equipment, training of operators, size of the system and time delay between end of processing and cleaning should be kept in mind when designing the cleaning SOP.
- The greater the risk of the product, or the greater the drug potency or toxicity, the more effort is required on the validation of cleaning methods.
- Pharmaceutical products can be contaminated by a variety of substances such as contaminants associated with previous products (both API and excipient residues), residues of cleaning agents, airborne matter such as dust and particulate, lubricants and ancillary material, such as disinfectants, and decomposition resides which include:
- Product residue breakdown occasioned by, e.g. use of strong acids and alkalis during the cleaning process.
- Breakdown products of the detergents, acids and alkalis that may be part of the cleaning process.
- The manufacturer should have a strategy on cleaning validation covering.
- Product-contact surfaces
- Cleaning after product changeover (when one pharmaceutical formulation is being changed for another, completely different formulation);
- Between batches in campaigns (when the same formula is being manufactured over a period of time, and different days). It seems acceptable that a campaign can last a working week, but anything longer becomes difficult to control and define.
- Bracketing product for cleaning validation. This often arises where there are products containing substances with similar properties (such as solubility) or the same substance in different strengths. An acceptable strategy is to manufacture the more dilute form (not necessarily the lowest dose) and then the most concentrated from. There are sometimes “families” of products which differ slightly as to actives or excipients; and
- Periodic evaluation and revalidation of the number of batches required should be included.
- At least three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.
- The practice of re-sampling should not be utilized and is acceptable only in rare case. Constant re-tasting and re-sampling can show that the cleaning process is not validated since these re-tests actually document the presence of unacceptable residue and contaminants from an ineffectual cleaning process.
- The Quality Unit and other appropriate management should formally approve the cleaning validation protocol.
- Records of the cleaning validation, which include all raw data of the test results together with, e.g. the cleaning record (signed by the operator, checked by production and reviewed by QA), should be kept and final validation report should be prepared. The final outcome should be stated, e.g. “all the acceptance criteria were met”
- Personnel/ operators who perform cleaning routinely should be trained and should have effective supervision.
Normally only cleaning procedures for product-contact
surfaces or the equipment need to be validated. Consideration should be given
to non- contact parts into which product or any process material may migrate.
Critical areas should be identified (independently from method of cleaning),
particularly in large systems employing semi-automatic or fully automatic
clean-in-place systems. Dedicated equipment should be used for products which
are difficult to clean equipment which is difficult to clean or for products
with a high safety risk where it is not possible to achieve the required
cleaning acceptance limits via a validated cleaning procedure.
Manufacturing Equipment & Rooms:
List of Areas/ unit that will be covered under Cleaning
Validation Programme
List of Manufacturing equipment (Area Wise)
Surface area of the equipments (Total area as well as
that coming in contact with the product)
Worst case Matrix
MACO calculations
Microbial Monitoring
This shall include:
Total Viable Microbial Count
Test for specified Micro organism
Revalidation
The revalidation of the existing system, facility,
equipment utility, process etc in necessary to maintain the validated status to
the plant. The criteria for revalidation is as follows:
The change in location of equipment from one location
to another.
The change in major part of critical equipment or after
a major breakdown of the critical equipment.
Change in the process & formula.
Change in the cleaning procedure or change in cleaning
agent.
Periodical revalidation.
Change in API.
Change in primary packaging.
Change in computer system.
Any change in that may have direct or indirect impact
on Quality attributes.
There are two basic categories or re-validation.
Re-validation in cases of known change (change having a
bearing on product quality). Including transfer of processes from one
pharmaceutical manufacturer to another, or from one site to another; and
Periodic re-validation carried out at scheduled
intervals.
Re-validation in cases of known change
- Processes and procedures should undergo periodic critical re-validation to ensure that they remain capable of achieving the intended results.
- It is necessary to ensure that changes in the process (whether intention or unintentional) do not adversely affect product quality or process characteristics. The nature of the changes that require re-validation should be stated in the VMP. Re-validation involves a repeat of the process validation.
- If any of the following are changed the process becomes invalid and the process could be viewed out of control, even if the finished product meets the marketing authorization specification for finished products:
- Changes of starting materials (physical properties, such as density, viscosity or particle size distribution may affect the process or product);
- Changes of starting materials (physical properties, such as density, viscosity or particle size distribution may affect the process or product);
- Transfer of processes to another site (change of facilities and installations which influence the process);
- Change of starting material manufacturer;
- Change of packing material;
- Change in process (e.g. mixing times);
- Change in the process (e.g. addition of automatic detection systems, installation of new equipment, major revisions to machinery or apparatus and breakdowns);
- Changes of equipment which involve the replacement of equipment on a “like-for like” basis would not normally require a re-validation. For example, a new centrifugal pump replacing an older model would not necessarily mean re-validation.
- Production area and support system changes (e.g. rearrangement of areas, new water treatment method);
- Appearance of negative quality trends; and
- Appearance of new findings based on current knowledge, e.g. Sterilization where the frequency of checking is dependent on sophistication of in-process methodology.
- Periodic re-validation is required as process changes may occur gradually over a period of time or because of wear of equipment. The decision on the time interval
- for re- validation is based in the results following review of historical data.
- The following points should be considered when periodic re-validation is performed:
- Review the master formula and specifications;
- Check the calibration records;
- Review the SOP;
- Review the cleaning records;
- Review the analytical method; and
- Review the records regarding planned preventative maintenance
Once the validation plan is made, specific validation
tasks are undertaken and documents are designed. Validation documentation shall
consist of validation protocol and validation report.
Validation Protocol shall be a written plan, which
outlines how validation shall be conducted including test parameters of
evaluation, involved equipment, acceptance criteria and revalidation criteria.
Validation Report shall scientifically evaluate the
data collected during the validation exercise; it shall also record the
conclusion and recommendation.
All validation and qualification documents shall be
prepared, checked and approved by the authorized personnel’s only.
Planning and scheduling
- All validation activities comprised in the VMP should be summarized and compiled in matrix format such matrix should provide an overview and contain:
- All items covered by the VMP that are subject to validation describing the extent of validation required [i.e. IQ, OQ and/or PQ.
- It should include validation of analytical techniques which are to be used in determining the validation status of other processes or systems.
- The validation approach, i.e. Prospective, Retrospective or concurrent.
- The Re-validation activities.
- Actual Status and future planning.
- An estimate of staffing (including training needs), equipment and other specific requirements to complete the project with detailed planning of subprojects. This time plan could be included in the matrix.
- The planning shall include to following aspects:
- List of products to be manufactured as attachment.
- Equipment / instruments Qualification Schedule.
- Measuring instrument calibration schedule.
- Laboratory Instrument validation / Calibration Schedule.
- Manufacturing Equipments Validation Schedule.
- Equipment / instrument preventive maintenance schedule.
- Environment Monitoring (General/ Microbial).
- Process Validation Schedule.
- Cleaning Validation Schedule.
- Training Schedule.
- Preparation of planning and Scheduling of VMP shall be from January to December of every year.
- In the last month/ quarter of current year, planning and scheduling for nest year shall be documented. This shall be considered as “Validation Master Plan” for next year.
- Any changes, revision, deletion, omission, submission in the same shall be through Change Control Proposal as an amendment.
- For preparation of VMP (Planning and Scheduling), completion, compliance, compilation and due date (s) for previous year (s) shall be considered.
- Regular calibration, validation and verification of all equipment, instruments and other devices used to measure the physical properties of substances, must be performed at regular intervals according to the SOPs (having regard to the extent to which they are used). The following are some examples:
- Balances.
- Infrared spectrophotometers.
- HPLC.
- UV spectrophotometer.
- Measuring Devices.
- Other instruments/ equipment.
- A calibration programme shall be available
- Equipment should be listed, together with the following information for each piece of equipment: calibration standards and limits, responsibilities for performing calibration, intervals between calibration, record-keeping requirements and logs, and actions to be taken when problems are identified.
- After calibration each piece of equipment, instruments and other devices under the control of the laboratory, and requiring calibration, should be labeled, coded or otherwise identified to indicate the status of calibration and the date when re-calibration is due.
- When the equipment, instruments and other devices are outside the direct control of the laboratory for a certain period of time, the laboratory should ensure that their function and calibration status are verified and shown to be satisfactory before they are taken into service again.
- There is a link between equipment calibration and preventative maintenance. Condition within calibration intervals.
- Personnel who provide calibration and preventative maintenance should have appropriate training.
- Routine Maintenance:
- All regular activity carried out a location
- Preventative maintenance assures that the equipment is in good working condition within calibration intervals.
- There shall be a preventive maintenance schedule available at the site.
- Maintenance Programme shall be followed as per the schedule date / month in the preventive maintenance calendar.
- Records shall be available in accordance with the schedule and the actual date of performing the preventive maintenance.
- The manufacturer should have a “change control” procedure.
- Change control is a formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state.
- Change control is an important element in any Quality Assurance system.
- Written procedures should be in place to describe the actions to taken if a change is proposed to a product component, process equipment, process environment (or site), method of production or testing or any other aspect that may affect product quality or support system operation. All changes should be formally requested, documented and accepted by representatives of production QC/QA, R&D, engineering and regulatory affairs, as appropriate.
- The likely impact (risk assessment) of the change on the product should be evaluated and the need for and extent of re-validation discussed. The change control system should ensure that all notified or requested changes are satisfactorily investigated, documented and authorized.
- Products made by processes subjected to changes should not be released for sale without full awareness and consideration of the change by the responsible staff.
- Standard operating procedures are prepared for all the activities carried out in the company to insure that all the employees are following approved system according to the cGMP norms.
Sanitization agents used for the purpose of
sanitization are validated.
Environmental Monitoring schedule
- Environmental monitoring shall be carried out as pre the standard procedure to ensure that the environment is controlled and maintained within the specified limits. This shall cover critical utility system, microbiology laboratory, process areas, washing areas and process corridors.
- cGMP (Current Good Manufacturing Practices) Training shall cover all the employees of the company. This includes all the modules of cGMP.
- Safety Training is conducted for all the employees of our company. This shall include all the modules of safety.
Equipment’s/ Instrument logbooks, area log books shall
be maintained independently of traceability purpose.
Intimation / Information of VMP
- Intimation/information of VMP shall be circulated to all concerned including, doers, reviewers and approvers of each activity.
- Qualification, Calibration, Validation activities to be performed by external agency shall also be communicated in appropriate format/ SOP as part of VMP.
- Head – QA or designee shall intimate to all concerned for VMP (Planning & Scheduling) for forthcoming month though electronic and/ or printed copies.
- This may be accompanied with required SOPs, protocol, format and instrument/ equipment etc. as applicable.
- All VMP activity shall be reviewed / verified by concerned and approved by appropriate authority within applicable and appropriate time frame.
- All VMP activities shall be recorded in applicable and appropriate electronic and /or printed forms with current version.
- Each VMP activity shall be reviewed / verified by concerned and approved by appropriate authority within applicable and appropriate time frame.
- Duly approved record (electronic and / printed form) of each VMP activity shall be submitted by performer/ doer to Head – QA or designee, with applicable time frame.
Completion, compliance and compilation of VMP (Planning
and scheduling) shall also be verified by Head-QA or designee as part of
self-inspection.
For preparation of next VMP (Planning and Scheduling),
such completion, compliance and compilation shall be considered.
