Process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Process validation is a requirement of current Good Manufacturing Practices (GMPs) for finished pharmaceuticals (21CFR 211) and of the GMP regulations for medical devices (21 CFR 820) and therefore applies to the manufacture of both drug products and medical devices.

Process validation involves a series of activities taking place over the lifecycle of the product and process.

The U.S. Food and Drug Administration (FDA) has proposed guidelines with the following definition for process validation: – “PROCESS VALIDATION” is establishing documented evidence which provides a high degree of assurance that a specific process consistently produces a product meeting its predetermined specifications and quality attributes.

The Process validation activities can be described in three stages.

Stage 1 – Process Design: The commercial process is defined during this stage based on knowledge gained through development and scale-up activities.

Stage 2 – Process Qualification: During this stage, the process design is confirmed as being capable of reproducible commercial manufacturing.

Stage 3 – Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

Types Of Process Validation

The guidelines on general principles of process validation mentions four types of validation:

A) Prospective validation (or premarket validation)

B) Retrospective validation

C) Concurrent validation

D) Revalidation

A) Prospective validation

Establishing documented evidence prior to process implementation that a system does what it proposed to do based on preplanned protocols. This approach to validation is normally undertaken whenever the process for a new formula (or within a new facility) must be validated before routine pharmaceutical production commences. In fact, validation of a process by this approach often leads to transfer of the manufacturing process from the development function to production.

B) Retrospective validation

Retrospective validation is used for facilities, processes, and process controls in operation use that have not undergone a formally documented validation process. Validation of these facilities, processes, and process controls is possible using historical data to provide the necessary documentary evidence that the process is doing what it is believed to do. Therefore, this type of validation is only acceptable for well-established processes and will be inappropriate where there have been recent changes in the composition of product, operating processes, or equipment.
This approach is rarely been used today because it’s very unlikely that any existing product hasn’t been subjected to the Prospective validation process. It is used only for the audit of a validated process.

C) Concurrent validation

Concurrent validation is used for establishing documented evidence that a facility and processes do what they purport to do, based on information generated during actual imputation of the process. This approach involves monitoring of critical processing steps and end product testing of current production, to show that the manufacturing process is in a state of control.

D) Revalidation

Revalidation means repeating the original validation effort or any part of it, and includes investigative review of existing performance data. This approach is essential to maintain the validated status of the plant, equipment, manufacturing processes and computer systems. Possible reasons for starting the revalidation process include:

  • The transfer of a product from one plant to another.
  • Changes to the product, the plant, the manufacturing process, the cleaning process, or other changes that could affect product quality.
  • The necessity of periodic checking of the validation results.
  • Significant (usually order of magnitude) increase or decrease in batch size.
  • Sequential batches that fail to meet product and process specifications.
  • The scope of revalidation procedures depends on the extent of the changes and the effect upon the product.

0
shares

  • vicky_yadav88

    is there any difference between process qualification and process validation?

  • Danielle Wood

    Great post. Unfortunately, a lot of products out today aren’t FDA regulated and people are getting sick from these drugs. It’s surprising how many places accept and display drugs that aren’t regulated by the FDA. I wish most of the drugs out now go through these processes of pharmaceutical manufacturing and process validation, because it would make all users feel safer. I still have to do my research every time I buy any type of supplement and I try to stick to FDA regulated supplements most of the time.

Similar articles:

Changes to equipment and documentation is an integral part of the whole GMP process in any regulated facility. In this article we will discuss how equipment is designed in a GMP facility and how good documentation practices are an essential part of quality assurance and GMP.

The content of this article has been taken from module 7 of our eLearning module on Good Manufacturing Practices (cGMP) within the life sciences.

You can view this module in full by viewing the video below.

cGMP eLearning Module – Compelling, Engaging and Interactive

 

Equipment

All equipment is designed, constructed and located to suit their intended use and to facilitate easy maintenance and cleaning.

Equipment is installed in such a way as to prevent any risk of error or of contamination, and cleaned according to detailed and written procedures and stored only in a clean and dry condition.

Production equipment should be designed in such a way as not to present any hazard to the products.

The parts of the production equipment that come into contact with the product must not be reactive, additive or absorptive to such an extent that it will affect the quality of the product and thus present any hazard.

Any defective equipment should, if possible, be removed from production and quality control areas, or at least be clearly labelled as defective. When not in use, equipment should be covered to ensure it remains clean.

Balances

Balances and measuring equipment of an appropriate range and precision should be available for production and quality control operations.

All measuring devices are required to be calibrated and checked at defined intervals by appropriate methods, and adequate records of such tests should be maintained.

Utilities

Fixed piping should be clearly labelled to indicate the contents and where applicable, the direction of flow.

Water pipes used in production (e.g. Purified Water, Water for Injection) are sanitised according to written procedures that detail the action limits for microbiological contamination and the measures to be taken.

Electrical circuits should be identified, and a record maintained of the load on each circuit to prevent inadvertent overload.

Documentation

Good Documentation Practices are an essential part of quality assurance and GMP.

It is important for a manufacturer to get the documentation right in order to get the product right.

GMP Documentation e.g. Site Master File, Specifications, Batch Manufacturing Formulae, Batch Manufacturing Records, Processing, Labelling, Packaging, Testing Instructions, Standard Operating Procedures, Protocols, Technical Agreements, Records, Certificates of Analysis, Reports etc. should contain the following attributes of a good document:

They should be:

  • Attributable
  • Legible
  • Contemporaneous
  • Original
  • Accurate
  • Complete
  • Durable
  • Corroborated
  • Version Based
  • Accessible
  • And Authorized

Change Control

Change to GMP documentation, equipment, processes, systems, instrumentation, test methods, etc. are required to be controlled under a formal change control program.

This program must consist of Quality oversight to review the proposed changes, evaluate the potential impact of the change, determine any potential risk to product quality, and to establish the required level of supplemental validation/documentation required for the change.

In many instances, changes will also require submission to the Health Authority for approval of the change.

For example, changes impacting the submission documentation are subject to post approval change guidances according to the Health Authority regulations.

Change Control is a critical aspect of the GMP systems.

If you want to learn more about cGMP or if you want to evaluate our eLearning module for your company you can find more information here.

0
shares

Similar articles:

The enduring assets of a laboratory’s work are the records that document those activities. When laboratory records are used to support a regulatory function, they are considered to be legal documents.

Laboratory Data Integrity – eLearning Course

 

For records to be considered reliable and trustworthy they must comply with the following criteria:

  • Legible and Understandable – they must be able to be read and understood for the lifetime of the record, without having to refer to the originator for clarification. The information may be needed in five, ten or twenty years’ time, perhaps after the originator is no longer available
  • Attributable – who made the record or created the data and when?
  • Contemporaneous – the record must be made at the time the activity was performed
  • Original – the information must not be written on a post-it, piece of scrap paper, sleeve of a lab coat etc. and then transcribed.
  • Accurate – no errors or editing without documented amendments
  • Complete – All the information and data associated with the analysis is included
  • Consistent – All elements in the sequence of analysis must be date & time stamped and must be in the expected order
  • Indelible – Records are made on to controlled documents, such as laboratory notebooks or controlled worksheets, or saved to electronic media
  • Available – over the entire lifetime of the record for review, audit and inspection

1. Legible and Understandable

A record that cannot be read or understood has no value and might as well not exist. All records should be composed so they conform to grammatical convention which should be consistent throughout.

It is best to avoid buzzwords, cliques and slang as these are prone to change with time and are often not understood outside a particular locality. It is always good practice to have any record reviewed by a second person as this can often highlight any ambiguities.

2. Attributable

The identity of the person creating a record should be documented. For paper records this is normally done by the individual signing and dating the record with their signature.

As the record you may be signing may be a legal document, you should clearly understand the implication of your signature. A signature should be individual to a specific individual and the practice of signing someone else’s name or initials is fraud, and is taken very seriously.

3. Contemporaneous

All records must be made at the time an activity takes place. Delaying writing up, for example until the end of the day, will inevitably affect the accuracy of that record as details can be forgotten or miss-remembered.

4. Original

All records must be original; information must be recorded directly onto the document. This avoids the potential of introducing errors in transcribing information between documents.

If information from an instrument is printed out, by the instrument, that printout is the original record and should be signed, dated and attached to the record.

5. Accurate

The record must reflect what actually happened. Any changes should be made without obscuring or obliterating the original information, the use of whiteout or correction fluid is prohibited.

Any changes made to a record should be signed by the person making the change and dated to show when it was made and a written explanation should also be provided. Remember, the record may be needed after you have left the company and cannot be contacted for clarification.

6. Complete

The record must contain all information associated with the analysis of the sample, including system suitability tests, injection sequences, processing methods, sample preparation procedures and results.
This must also include any reinjections or repeat analysis performed on the sample.

Remember the position of the regulatory authorities for something that needs to be done is – ‘if it isn’t documented it’s a rumour’. However, failing to disclose reanalysis or reinjection of samples will undermine confidence in the reliability of the records.

7. Consistent

Consistency in this context refers to the sequence of the component events, which the analytical method comprises, being performed in a logical order.

For example it is not possible to commence the HPLC run before the samples have been prepared, therefore the balance printout for the sample weights should be date/time stamped at least one or two hours prior to the sample injection time, to allow time to prepare the samples. Therefore all date/time stamps should be in the expected sequence.

In order to avoid confusion in this respect, it is worth ensuring all instruments that produce date/time stamped printouts are time synchronised. This is best done by reference to a standard reference time, such as a national online time server.

8. Indelible

Indelible means the record must be legible for the lifetime of the record and once it has been made it cannot be removed.

Hand written entries of information should be made in ink and not pencil which can be erased

If printouts are made on thermal paper, which darkens with time, a photocopy should be made; this should be certified as an accurate copy of the original print and attached

If print outs are attached to a page they should be

  • Secured to the page with acid free glue and industrial strength Sellotape
  • Signed and dated across the attachment and the page
  • Annotated with a reference to the document

9. Available

All records should be available for inspection, audit and review for the lifetime of the document. If a document is requested during a regulatory audit, it should be produced within thirty minutes.

Therefore, the laboratory should establish an easy to reference archive system. Records should be archived so as to preserve their integrity, such as

  • Secure facility with restricted access
  • Effective fire suppression
  • Protection from dampness or humidity
  • Controlled access to Document

Check Out Our Laboratory Data Integrity eLearning Module

If you are looking for a way to train your staff on the importance of data integrity in a regulated environment check out oureLearning Course.

0
shares

Similar articles: