Global Regulations: Production Record Review

Production Record Review deviations are the most frequent GMP observations made by the regulatory agencies across the globe. They are cited as GMP deficiencies. A Batch Processing Record or Production record is the main document that shows the quality of the manufacturer complying with all the regulatory guidelines and process consistency that is developed by the manufacturers. Once it is signed by the manufacturing professional of an organization and released it is legally binding.

Care must be taken to review each and every batch record regarding the missing entries and also the discrepancies that are encountered during manufacturing of a registered Pharmaceutical, Biopharmaceutical or Medical device product. This is not just limited to the above said fields but also it implies to neutraceutical supplements too.

Various regulatory agencies have clearly stated the guidelines and the regulations involved in the review of such documents.

US FDA :Subpart J–Records and Reports Sec. 211.192 Production record review.

This states the requirements for the review and approval of production and control records, including the requirements for the investigation of any unexplained discrepancies.

All drug product production and control records, including those for packaging and labeling, shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Any unexplained discrepancy (including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records) or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed.

The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy. A written record of the investigation shall be made and shall include the conclusions and follow up.

Similar citations are also observed in EU GMP.

Chapter 1. Quality Management systems

Product Quality Review

Regular periodic or rolling quality reviews of all licensed medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product to highlight any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews, and should include at least:

Global Regulations: Production Record Review

(i) A review of starting materials including packaging materials used in the product, especially those from new sources.

(ii) A review of critical in-process controls and finished product results.

(iii) A review of all batches that failed to meet established specification(s) and their investigation.

(iv) A review of all significant deviations or non-conformances, their related investigations, and the effectiveness of resultant corrective and preventative actions taken.

(v) A review of all changes carried out to the processes or analytical methods.

(vi) A review of Marketing Authorisation variations submitted/granted/refused, Including those for third country (export only) dossiers.

(vii) A review of the results of the stability monitoring programme and any adverse trends.

(viii) A review of all quality-related returns, complaints and recalls and the investigations performed at the time.

(ix) A review of adequacy of any other previous product process or equipment corrective actions.

(x) For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.

(xi) The qualification status of relevant equipment and utilities, e.g. HVAC, water, compressed gases, etc.

(xii) A review of any contractual arrangements as defined in Chapter 7 to ensure that they are up to date.

Chapter 4: Documentation

Point 4.3 Documents containing instructions should be approved, signed and dated by appropriate and authorised persons. Documents should have unambiguous contents and be uniquely identifiable. The effective date should be defined.

4.24 There should be written procedures for the internal labeling, quarantine and storage of starting materials, packaging materials and other materials, as appropriate.

Chapter 5: Production

5.8 Checks on yields, and reconciliation of quantities, should be carried out as necessary to ensure that there are no discrepancies outside acceptable limits.

5.39 Any significant deviation from the expected yield should be recorded and investigated. (Processing operations of Intermediates and bulk drugs)

Chapter 9. Self Inspection

9.3 All self-inspections should be recorded. Reports should contain all the observations made during the inspections and, where applicable, proposals for corrective measures. Statements on the actions subsequently taken should also be recorded.

Health Canada Guidelines 2009

(Documentations and Records) Batch Production Record Review : Published from ICH Q7A.

6.70 Written procedures should be established and followed for the review and approval of batch production and laboratory control records, including packaging and labelling, to determine compliance of the intermediate or API with established specifications before a batch is released or distributed.

6.71 Batch production and laboratory control records of critical process steps should be reviewed and approved by the quality unit(s) before an API batch is released or distributed. Production and laboratory control records of non-critical process steps can be reviewed by qualified production personnel or other units following procedures approved by the quality unit(s).

6.72 All deviation, investigation, and OOS reports should be reviewed as part of the batch record review before the batch is released.

6.73 The quality unit(s) can delegate to the production unit the responsibility and authority for release of intermediates, except for those shipped outside the control of the manufacturing company.

WHO guidance:

Annex 4 : Good Manufacturing Practices for pharmaceutical products: main principles

Batch record review: Production and quality control records should be reviewed as part of the approval process of batch release. Any divergence or failure of a batch to meet its specifications should be thoroughly investigated. The investigation should, if necessary, extend to other batches of the same product and other products that may have been associated with the specific failure or discrepancy. A written record of the investigation should be made and should include the conclusion and follow-up action.

Good practice in Production Chapter 16:

Checks on yields and reconciliation of quantities should be carried out as necessary to ensure that there are no discrepancies outside acceptable limits.

Any significant deviation from the expected yield should be recorded and investigated.

Good practices in quality control: Records must be made of the results of inspecting and testing the materials and intermediate, bulk and finished products against specifications; product assessment must include a review and evaluation of the relevant production documentation and an assessment of deviations from specified procedures

ICH Q7A (working Document) GMPs for APIs

During a batch record review check for

  • Missing records and out-prints
  • Incomplete entries
  • Illegible corrections
  • Equipment maintenance, breakdown and replacement
  • Valid calibrations and service intervals of test equipment (as a useful cross check to routine control of test equipment)
  • Reports on OOS-results
  • Completeness of deviation reports
  • Impact of reported deviations on product quality
  • Compliance with specifications, parameter ranges or acceptance criteria including tighter customer specifications

GOVERNMENT OF INDIA: The Drugs and Cosmetics act. (Revised 2005) Schedule M

Quality Control:
To review production records to ensure that no errors have occurred or if errors have occurred that they have been fully investigated.

Documentation and Records:

Documentation is an essential part of the Quality assurance system and, as such, shall be related to all aspects of Good Manufacturing Practices (GMP). Its aim is to define the specifications for all materials, method of manufacture and control, to ensure that all personnel concerned with manufacture know the information necessary to decide whether or not to release a batch of a drug for sale and to provide an audit trail that shall permit investigation of the history of any suspected defective batch.

12.1 Documents designed, prepared, reviewed and controlled, wherever applicable, shall comply with these rules.

12.2 Documents shall be approved, signed and dated by appropriate and authorized persons.

12.3 Documents shall specify the title, nature and purpose. They shall be laid out in an orderly fashion and be easy to check. Reproduced documents shall be clear and legible. Documents shall be regularly reviewed and kept up to date. Any alteration made in the entry of a document shall be signed and dated.

12.4 The records shall be made or completed at the time of each operation in such a way that all significant activities concerning the manufacture of pharmaceutical products are traceable. Records and associated Standard Operating Procedures (SOP) shall be retained for at least one year after the expiry date of the finished product.

12.5 Data may be recorded by electronic data processing systems or other reliable means, but Master Formulae and detailed operating procedures relating to the system in use shall also be available in a hard copy to facilitate checking of the accuracy of the records. Wherever documentation is handled by electronic data processing methods, authorized persons shall enter or modify data in the computer. There shall be record of changes and deletions. Access shall be restricted by ‘passwords’ or other means and the result of entry of critical data shall be independently checked. Batch records electronically stored shall be protected by a suitable back-up. During the period of retention, all relevant data shall be readily available.

The whole set of regulations gives us the importance of a proper Production Record review process. This can be only achieved by robust Batch Record solutions and proper training and methodology that a qualified person follows in the industry. It’s an important responsibility for a qualified person.


Durga Prasad
GMP Specialist

Comments are closed.

Join Our Newsletter

Our Networks

Facebook Twitter LinkedIn Youtube