By Mustafa Edik

If you are the chief executive officer of a successful pharmaceutical company, you need to know that your company is meeting and exceeding customer expectations. But first, do you even know who those customers are? Your customers may be consumers of the product, patients and doctors, purchasers (managed care), shareholders, or regulatory authorities. In fact, all these types of people may be your customers. Although their needs will vary, your company has the common goal of fulfilling all their expectations.

There are different ways to determine customer expectations, but without an adequate evaluation tool, a standardized comparison to a common reference point cannot be made. Current regulations for medical devices (21 CFR part 820) and good laboratory practices (21 CFR part 58 and 40 CFR part 160) include requirements for formalized, well-established, and well-maintained internal auditing programs. Current expectations of most other FDA-regulated industries, such as biotechnology and pharmaceuticals, are no different, although the regulations do not specifically mandate the installation of an internal auditing program. It is only a matter of time before these requirements are more clearly defined and codified in these and other areas.

Traditional good manufacturing practices (GMP) audits by the compliance unit conclude with the issuance of observations. The observation responses are evaluated for acceptability and the file is closed.

The time to eliminate the stigma surrounding internal GMP audits has arrived. Historically, internal GMP audits have carried a negative connotation because they are typically performed in an adversarial manner. Changing the objective of GMP auditing from identifying deficiencies to assessing and enhancing quality would go a long way in shifting the perspective most companies have of internal GMP audit programs. These audits should be viewed as an assessment of compliance to regulatory requirements and as one facet of overall quality.

There are several reasons for instituting an internal GMP audit program, including:

• Increase the potential for early identification of regulatory concerns based on FDA interpretations and current compliance focus
• Identify compliance deficiencies and deviations from industry standards and company requirements
• Provide a benchmark of compliance with other companies and regulatory expectations
• Inform management of compliance status, regulatory risk, and civil liability
• Foster continuous improvement and forward quality
• Provide a tool by which the company can stay ahead of rapidly increasing regulatory demands

Essential requirements for a successful internal quality/compliance GMP audit program are as follows:

• Total commitment by the executive management team to quality and the GMP audit program
• An adequate number of qualified personnel well-suited to conduct internal quality and GMP compliance audits
• Established standards against which to audit
• An independent reporting structure directly responsible to executive management with the authority to allocate resources
• The resources (economic, personnel, time) to support the program’s and operation’s ongoing needs

Be prepared

A GMP internal audit’s success often hinges on preparation. Generally, an extensive GMP internal audit requires considerable preparation to identify opportunities for mutual gain. Before a GMP internal audit begins, you should make sure that you know the procedures better than the supervisor of the department being audited.

Poor preparation wastes time and can make you look like a phony. Don’t embarrass yourself by pointing out discrepancies that aren’t really problems. You should also make sure that the time chosen for the GMP internal audit is convenient for the supervisor. A good working relationship is built on trust, and one way to enhance that trust is by being punctual. No one appreciates having his or her time wasted. Being prepared and on time are common courtesies that, if overlooked, will likely guarantee that the GMP internal audit will get off to a bad start.

Scheduling

First, begin with the yearly GMP audit schedule. Involve as many of the auditees as practical. Take into account the strategic issues and once you are finished, stick to the plan (as best you can). Make sure all lines of communication stay open and the auditees are continually informed of the plan.

On the tactical side, once you have your GMP audit plan and schedule developed for the actual GMP audit, ensure it is communicated to all concerned. Make sure you have enough GMP auditors and they are prepared well in advance, so you can maximize the time allocated to the GMP audit.

Keeping to the GMP audit schedule can be tough at times. GMP auditors must do their best to maintain the schedule. When this is not possible, the auditees need to be informed. If you are scheduled to be in QC lab at 1:00 and don’t arrive until 3:00, the GMP audit will probably not be as effective as you would desire.

Ask the right questions

Asking the right question begins in the preparation phase of the GMP audit. An understanding of the requirements, the standard operating procedures, work instructions, and forms play a major role in asking the right questions. Use this information to generate a checklist that is meaningful. Before the GMP audit, you should know what you are going to ask and what evidence you will be looking for.

GMP audits can be disturbing, so keep in mind the reason for the GMP audit review of pharmaceutical quality management system (ICH Q10), not the auditee. Remember, your role is to identify areas for improvement, and you therefore must avoid an atmosphere of blame.

Ask one question at a time and listen for the answer. Don’t be surprised if the auditee answers question one and question four in their response. If you actively listen you will know they answered question four, but if you are too busy thinking about the next question you will not. Later, if you ask question four after they have already answered it, the auditee will be irritated with you.

Likewise, the auditee might answer the wrong question, or their answer might have nothing to do with the question asked, which may be due to their lack of understanding. Your question must be clear to the auditee.

Make sure your questions are understandable. Avoid leading questions, where the answer is part of the question: “Now, your management review meetings are scheduled for every three months, right?” Avoid questions that have no correct answer. Questions also must not be accusatory in any way.

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About the author

After graduation as a Chemist from University, Mustafa Edik began his more than 23 years of career as a laboratory supervisor with Bayer. After 15 years of working as a quality assurance assistant manager, laboratory supervisor, and pharmaceutical quality management systems and GMP lead auditor, he decided to continue his career as a consultant. He has served with the Turkish Atomic Energy Authority (TAEA) as principal GMP auditor and consultant for six years. TAEA was audited by Republic of Turkey Ministry of Health and granted a GMP certificate for five radiopharmaceuticals. This success has won great acclaim in all health authorities and industry. He has prepared and presented various trainings and workshops to more than 7,000 individuals from 100 international and local pharmaceutical, medical device, and cosmetics companies on GMP, GDP, and pharmaceutical quality management systems. He took part in several international pharmaceutical facility establishment projects as a GMP consultant. He set up various quality management systems to local pharmaceutical and medical device companies. During his time as vice president of quality and technical operations at the Quality Academia training and consultancy firm, Edik acquired and convert it to a completely Turkish company. As an only IRCA-certificated pharmaceutical quality management systems and GMP lead auditor in Turkey, he currently conducts API, Excipient, packaging materials suppliers and manufacturers, third-party logistics service providers, and sterile and non-sterile manufacturing facilities audits according to FDA, EMA, PIC/S, TMMDA, MHRA, TGA Health Canada, and WHO regulations and guidelines. He finished his second university degree in biopharmaceutical sciences BSc (Hons) in 2019.