Water systems are one of the most important systems in the pharmaceutical industry. What are the GMP requirements for the qualification and running of these systems? The US GMP regulations (21 Code of Federal Regulation (CFR) 210/211) do not provide much concrete information on this. There is still a Guide to Inspection for FDA inspectors from the early 90s. So, what does the FDA expect today? A current Warning Letter provides a few answers.
When it comes to process validation, FDA's Process Validation Guidance from 2011 is state-of-the-art. It is interesting to see how the FDA would like to see the guidance implemented. Here, the findings described in Warning Letters issued after FDA inspections can help. A recent Warning Letter regarding deficiencies to 21 CFR 211.100 from October 2019 mentions the following.
Data Integrity for Analytical Instruments connected to a LIMS via a Middleware
The data integrity topic raises a number of questions. Current questions are addressed in a loose sequence of News. Question 6: How can I handle analysis devices that are connected to a LIMS via a middleware? The manufacturer does not allow access to the original data in the automated analyser though.
Warning Letter: Deficiencies in Validation and OOS
Once again, an Indian pharmaceutical manufacturer has received a Warning Letter from the US-American FDA due to deficiencies discovered during an inspection. The Letter focuses on deficiencies in the validation and the handling of OOS results in the laboratory. Read more here
EMA website on Permitted Daily Exposure (PDE) limits
The issue of cross-contamination has been addressed by authorities since the publication of the first edition of the EU GMP Guidelines. The EMA has compiled everything essential on health-based exposure limits and PDE limits on their website.
New Ph. Eur. chapter on statistical process control (SPC) planned
Process controls have become customary in pharmaceutical processes. The aim is to monitor a process and improve it if possible. Statistical process control (SPC) is viewed as one option to implement Ongoing/Continued Process Verification. PharmEuropa has now published a new draft chapter on the topic.
Fundamental GMP Deficiencies at US-American Pharmaceutical Manufacturer
During the inspection of a pharmaceutical manufacturer in the USA, the FDA discovered fundamental GMP deficiencies which concern - among other things - cleaning of equipment, cleaning validation, the water system and the stability programme.
With the revision of Annex 15 in October 2015, the topic of requalification has become more important. Time intervals for the assessment of the equipment with regard to the qualification status and for the requalification itself should be justified. Criteria for the assessment should be defined. This is sometimes difficult. Chapter 9 of the revised ISPE Baseline No 5 Commissioning & Qualification of June 2019 on the periodic review can be helpful here.
The GMP regulations do not provide any concrete specifications for the calibration of weighing instruments. They refer to suitable measuring and weighing ranges and the required accuracy. Regular maintenance and calibration are also required. So how can these general formulations be interpreted?
Warning Letter due to Deficiencies in the Purified Water System
In June, a US-American pharmaceutical manufacturer received a Warning Letter from the FDA due to deficiencies in the Purified Water System which concern - among other things - the design of the water system, monitoring, sampling and handling of CAPAs.
ISPE publishes revised Guideline on Commissioning and Qualification
The ISPE Baseline Guide Vol. 5 on Commissioning & Qualification has been in place since 2001 and was thus no longer up to date. Recent developments, e.g. towards a lifecycle model, were not reflected in the document. Now the ISPE Baseline Guide Vol. 5 has been completely revised.
Regulations concerning the handling and management of data from "small" computerised systems?
The data integrity topic raises a number of questions. Current questions are addressed in a loose sequence of News. Question 5: Are regulations necessary for the handling and management of data generated by small systems (e.g. pH meters, filter integrity testers, etc.)?
What is considered GMP-compliant equipment design?
It's a frequent question what GMP compliant equipment design is or how a system has to be made up in order to be GMP compliant and suitable for the manufacturing of medicinal products/APIs. There is a short and a long answer to these questions around GMP-compliant equipment design.