The most important word in the pharmaceutical industry. Usually number of audit concluded based on the “What” and How? Few important examples are quoted below,
What is the equipment requalification frequency?
What is the HEPA replace frequency?
What is the calibration frequency?
Once you provide the reply of their next question will be, how you finalized the frequency?
We reply with following statement,
As per operating procedure,
As per vendor recommendations,
As per historical data,
As per risked based approach,
As per criticality assessment,
As per Validation master planner schedule
Before specifying any requirement in the operating procedure, we should think the based on the patient safety only. Outcome of cGMP practices is to produce safe, efficacious, pure medicines.
Operating procedure play major role in the audit. We are least bother to prepare a good SOP (standard operating procedure), mostly SOP’s are copy and pasted from another source. To develop a good SOP needs 2-3 days at least but the expectation of senior management is to prepare or finalized 100 SOP’s within a month of time duration. Apart from the author rarely anyone read/reviews it in details. Author rely on the reviewer, reviewer rely on author and Quality Assurance relay on reviewer and author. Finally based on the trust SOP get approved. But problem identify during audit, most of the cases team leaders read the SOP first time in details in front of auditor during inspection.
Following the most critical SOP’s/procedure get scrutinized during audit,
Environment monitoring procedure and trending
Water sampling, monitoring and trending
Calibration procedure
Break down maintenance procedure
Management of filters
Management of gases
Qualification and validation program
Software application usages procedure and in compliance with 21CFR part 11 in QC and manufacturing
Cleaning and disinfection procedure
Media fill management
Training management and job allocation
Document issuance, distribution, retrieval and archival procedure
Equipment and instrument specific operation, calibration and maintenance procedure
Deviation/ Incident / Change management
OOS/ OOT handling procedure
Next part is Policy or Apex documents and drawings (Layouts and P&ID’s). These documents are made one time only, then it revised based on the audit observation. During revision review was performed in the proposed change part only, entire document never read latter on by any one. Examples are like Site master file, Validation master plan, Quality policy, we can call those as foundation document of any industry.
Similar for P&ID’s and layouts of system, equipment, system and area. Drawings are prepared initially but not reviewed periodically. During audit, lots of changes are identified inform of the auditor. Most of the layouts are revised after announcement of audit or during audit, so currently signed drawings are submitted for audit purposes.
One of the major painful area is Batch manufacturing record and packing record filling, which are too much descriptive and sometime contains number of duplicate information. Most of the firms maintained area monitoring logbooks, equipment usages logbooks in the shop floor but again we copied the same information in the batch record. Batch record and SOP both are updated with equipment operating recipes including validated parameter details. Approaches need to follow to identify Material Attributes and Process Parameters, same need to be documented in the batch manufacturing record.
Step 1:
Identify drug product CQA’s
Step 2:
For each process step, identify intermediate COAs that impact drug product CQAs
Step 3:
Identify material attributes and process parameters that may impact the intermediate CQAs of the process step
Useful tools: Risk assessment, prior knowledge, established science
Batch can be released statically based on the outcome obtained by using Process Capability & Performance (Pp, Ppk, Cp, Cpk).
In this article, we have focused on some of the critical part of our pharmaceutical industry. In most of the audits we faced difficulties to handle those areas.