SOP for Reprocessing, Reworking and Recovery of Drug Products

In short: This is an illustrative SOP template for handling reprocessing, reworking and recovery of drug products at a manufacturing site. It separates the three terms, sets approval, risk assessment, batch suffix and stability rules, and keeps records linked to the original batch. Limits such as the 6-month recovery period are example site rules, not regulatory requirements.

Note: This is an example SOP. Numbers (such as QA006, QA007), time limits and batch-number suffixes are site choices. Adapt them under your own quality system and licence conditions.

Regulatory background

• EU GMP Chapter 5 (revision effective 1 March 2015), paragraphs 5.66 to 5.69: rejected products may be reprocessed only exceptionally, if final quality is not affected, specifications are met, a defined and authorised procedure is followed after risk evaluation, and records are kept (5.67). Recovery of conforming earlier batches into a batch of the same product at a defined stage must be authorised beforehand, follow a defined procedure, consider the effect on shelf life and be recorded (5.68). QC should consider whether extra testing is needed (5.69).
• ICH Q7 (Step 4, 10 November 2000) sections 14.2 to 14.4 cover reprocessing, reworking and recovery of materials and solvents, but for active pharmaceutical ingredients, not finished dosage forms. Use it only as an analogy for drug products.
• WHO glossary definitions (WHO TRS 986, Annex 2, 2014) are the source of the definitions below for medicinal products.

1. Objective

To lay down a procedure for reprocessing, reworking and recovery of drug products.

2. Scope

This SOP applies to reprocessing, reworking and recovery of drug products at different stages of manufacture at the manufacturing facility.

3. Responsibility

• An authorised designee of Quality Assurance prepares and reviews the SOP.
• Manager QA or authorised designee approves the SOP and ensures its effective implementation.

4. Procedure

4.1 General requirements

1. Reprocessing, reworking or recovery is done only where there is a specific need, with prior approval of Manager QA, the customer and Regulatory Affairs (RA).
2. The batch is released only if the quality of the final product is not affected and specifications are met.
3. A risk assessment is done before starting a reprocessed, reworked or recovered batch, as per the current Risk Assessment SOP (No. QA006).
4. Additional testing of in-process stages or finished product is done where justified.

4.2 Reprocessing

Definition: Subjecting all or part of a batch or lot of an in-process stage or finished product of a single batch to a previous step of the validated manufacturing process because it failed predetermined specifications. It is normally a repeat of a step already in the process.

4.3 Reworking

Definition: Subjecting an in-process stage or finished product of a single batch to an alternate process because it failed predetermined specifications. Reworking is a new step that is not part of the standard process.

4.4 Recovery

Definition (site wording): Recovery means collecting residue or material from a stage of a batch and adding it back into a later batch of the same product at a defined stage. EU GMP 5.68 describes this as incorporating earlier conforming batches (or parts) into a batch of the same product at a defined stage.

1. In-house procedure (not a pharmacopoeial or ICH Q7 / EU GMP requirement): recoverable material is stored for not more than 6 months. If it is not used in that time, it is destroyed.
2. Justification for the holding time: a hold time for recovered or reprocessed material must be supported by real-time (or hold-time) stability data generated under the actual storage conditions. Accelerated stability data alone can support, but cannot by itself justify, the 6-month holding period.
3. Recoveries from different operating cycles are collected separately for each batch.
4. Recoveries are collected batch-wise in clean containers with a status label showing product name, batch number, manufacturing and expiry dates, drum number, quantity in each drum, signature and date.
5. When recovery is added to a normal batch of the same product, that batch is charged for accelerated stability and the batch record is stamped as per QA007.
6. Any material left over from reprocessing or recovery that is not used in the batch must not be used in any later batch. It is destroyed, and the destruction is documented.
7. Recoverable residue of any stage is tested as per the standard test procedure, including impurities where applicable, before it is added. Results are compared with the initial results. If there is no significant change, it may be used. Production informs QC if fresh raw material is added.
8. The processing date of the recovery batch is its manufacturing date. The expiry date of the oldest recoverable residue is the expiry date of the recovery batch.
9. Recovered material is added during dry screening after milling. The granules are sampled and analysed after adding recovery, before the next step. (This is specific to granulated products.)
10. Recovered material older than 6 months is destroyed with approval of Manager QA and authorisation of the technical director, and the destruction record is kept.
11. Rejected recovered material is not added to regular batches.
12. Add suffix “R” to the batch number of a recovered batch.
13. Attach the recovered batch record to the record of the original batch.

4.5 Licence restriction

No reprocessing, reworking or recovery is done at the site for any product covered by a PL/MA (product licence / marketing authorisation) that does not permit it. Where an approved licence or authorisation does not describe the reprocessing or recovery step, a regulatory assessment and, if needed, a variation are required first.

5. Training

• Trainer: Head - Quality Assurance
• Trainees: Departmental and sectional heads of QA and Production

6. Distribution

7. Annexures

• Annexure I: Reprocessing approval form
• Annexure II: Reworking approval form
• Annexure III: Recovery approval form

8. Abbreviations

QA: Quality Assurance; QC: Quality Control; RA: Regulatory Affairs; R&D: Research and Development; PL/MA: product licence / marketing authorisation; NMT: not more than.

Frequently asked questions

What is the difference between reprocessing and reworking?

Reprocessing repeats a step of the validated, approved process. Reworking uses a different, alternate process that is not part of the standard process.

Can any batch be reworked?

Only with a prior investigation, risk assessment, approval, and where the licence or regulatory approval allows it. The reworked batch must meet specifications.

Is there a regulatory limit on how long recovered material may be kept?

Not in the texts checked. The 6-month limit here is a site rule that should be justified by data.

References

1. European Commission, EudraLex Volume 4, EU GMP Part I, Chapter 5: Production (revision effective 1 March 2015), paragraphs 5.66 to 5.69.
2. ICH Harmonised Tripartite Guideline Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, Step 4 version dated 10 November 2000, sections 14.2 to 14.4 (APIs only).
3. WHO Technical Report Series No. 986, Annex 2: WHO good manufacturing practices for pharmaceutical products: main principles (2014), glossary.
4. CDSCO, Revised Schedule M (G.S.R. 922(E), 28 December 2023). Readers should verify the requirements against the current revised Schedule M (G.S.R. 922(E), 28 December 2023) text.

Revision history