Mark Stevens and Tony Gasson, GxP Consulting, look at how the services of the Qualified Person (QP) can be maximised to beyond that of purely achieving final product release
Complying with current regulations within the pharmaceutical industry is an increasingly complex and rigorous process as regulatory bodies continue to step up the already stringent rules put in place to protect public safety. To ensure that a new medicinal product passes all legal checks, pharmaceutical companies must invest considerable resource and expertise in research, development and manufacturing processes.
Under EU regulations,1 pharmaceutical companies must also employ the services of at least one QP to ensure all manufacturing procedures, paperwork, quality controls, storage systems and the medicinal product itself meets the legal standards required.
The concept of the QP role was first introduced in 1975 and is a mandatory requirement for companies involved in the manufacture of both human and veterinary medicinal products. In a number of cases, especially with smaller pharmaceutical companies, a contracted QP provides the service. A contracted QP has the same responsibilities and duties as an in-house QP, but is not permanently employed by the pharmaceutical company.
The importance of the QP role is reflected in the regulations governing the qualifications and experience of a candidate. Article 49 of EU Directive 2001/83/EC states that a QP must have at least one formal qualification in pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry or biology, as well as a minimum of two years" experience in qualitative and quantitative analysis of medicinal products.
In practice, most QPs have at least 10 years" experience in a company (2-5 years with production and 2-5 years with quality, both QC and QA). They attend 2-3 years of specialist courses that cover a broad range of topics, such as the legal aspects, statistics, engineering and management studies. They have to become people "aware" and able to assess honesty, integrity and probity to ensure they make their decisions as carefully and accurately as possible.
Due to the complex criteria a candidate must fulfil to become a QP, an official register has been created and only certified candidates from the register can be employed in the QP role. In the UK, The Royal Society of Chemistry, the Institute of Biology and the Royal Pharmaceutical Society of Great Britain jointly assess the eligibility of their members for QP status on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA) of the Department of Health, and the Veterinary Medicines Directorate (VMD) of the Department of the Environment, Food and Rural Affairs (DEFRA).
the QP's role
A QP is responsible for certifying every batch of a pharmaceutical product for release to market.2 It is the QP's responsibility to ensure that every stage of the manufacture of a new drug meets all required legislation relating to Good Manufacturing Practice (GMP). The Rules and Guidance for Pharmaceutical Manufacturers and Distributors, more commonly referred to as The Orange Guide, collates European and UK guidance documents and information on legislation relating to the manufacture and distribution of medicines for human use. The guide features all EU regulations for GMP, detailed EU directives and a code of conduct for QPs to follow. Similar regulations are employed in other countries.
Rather than focusing entirely on the sampling of products, GMP regulations take a more holistic approach and relate to the whole manufacturing and laboratory-testing environment.
To pass a batch of new product as suitable for release to market, a QP must be satisfied that the manufacturer has suitable premises, equipment and staff to meet regulatory guidelines. The QP is also responsible for establishing and maintaining a system of complete transparency at all times. This means that all data on both the manufacturing processes and the drug itself, including perceived risks, must be carefully recorded and readily available for inspection. A QP must prepare regular reports for governing authorities and ensure that any request for information by regulatory authorities is fully answered. Detailed records (including reference samples of the product itself) must also be kept on every single batch of drug that is certified by a QP.
If a product is found to be in breach of any legislation, the company responsible for its release would face serious repercussions. In July 2007, the former head of China's state Food and Drug Administration, Zheng Xiaoyu, was executed after being found guilty of accepting bribes from pharmaceutical companies to register their products without making them undergo the necessary checks. The bribes were linked to the release of several dangerous products onto the market that were believed to be connected with the deaths of many people. Although an extreme example, Zheng Xiaoyu serves as a reminder of the importance of regulatory compliance and the life-threatening consequences if companies fail to adhere to the legislation.
As well as ensuring that Quality Management Systems (QMS) are operational and each batch of drugs meets the required standards, a QP must also consider wider technical, ethical and professional obligations in terms of patient safety, quality and efficacy. A Code of Practice has been designed to take account of these issues. The Code of Conduct supports the legal framework provided by EU directives and sets out operational guidelines for carrying out the functions of a QP. A QP has a similar background to a Regulatory Inspector and acts as the company's internal Inspector. All Inspectors now are QPs and have worked previously in this capacity for pharmaceutical companies.
QP vs manufacturer
Both pharmaceutical manufacturers and QPs have a duty to ensure that patients are properly protected and that medicinal products meet all requirements for safety, quality and efficacy.3 Despite this shared duty, there remains a perceived conflict of interest between the QP and a pharmaceutical company looking to release a new drug onto the market.
While both must consider patient safety, a pharmaceutical company must also focus on profit. To ensure the pharmaceutical company makes maximum profit when manufacturing drugs, the cost of the entire manufacturing process is carefully mapped out from start to finish. This means that the company effort focuses on getting a drug to market as efficiently and cost-effectively as possible.
The primary legal responsibility of a QP is to certify each batch prior to release. If required standards are not met at anytime during the manufacturing process, the QP has the power to reject a batch for release or even halt production all together. This can have massive cost implications for a company as more money may have to be spent on correcting any problems and then restarting the manufacturing process. Company profits are often calculated on a batch by batch basis; therefore, if any batch is rejected it would reduce the profitability of the product and hence the company. If the release dates for a new drug have to be pushed back or scrapped altogether it has dramatic financial implications for the business.
The careful documentation of each step of drug manufacture and testing processes are crucial elements and are necessary to show exactly how the product was made and tested. If all documentation is not in order, the product will be rejected automatically and the whole manufacturing process must be started again.
The challenge for the pharmaceutical company is to establish QMS in the early stages of process development to ensure that all legal standards and regulations are fully adhered to before any manufacturing has begun. This will help to maximise the chances of getting the manufacturing process correct and compliant with all regulations as quickly as possible although both QPs and pharmaceutical companies alike will concede that getting it right first time is rare.
There is a belief in some pharmaceutical organisations that employing a QP serves only to increase costs and prolong the entire manufacturing process. They often overlook the long-term benefits and knowledge that a QP can bring if recruited onto a project early enough in the process.
Many companies employ a QP on a part-time basis and typically focus on the final product release in order to get to release stage as quickly and cheaply as possible.
Although QP involvement early in the manufacturing process will increase initial set-up costs, it can actually result in a long-term cost saving. A QP brought in early on in the design stage can draw on expertise in research, production, QC and project management to offer sound advice on implementing the necessary systems before the actual manufacturing process is started. A company that adapts the QP ethos when putting the manufacturing system in place is far more likely to get a drug through to release stage with the least amount of reworking possible. Rework means cost. By investing time and resources into the plant and production processes earlier, in line with regulatory guidelines, the chances of manufacturing being stopped or delayed by the QP is massively reduced. This also reduces the chance of additional costs being added to the final budget.
Similarly, utilising the knowledge, experience and regulatory compliance understanding of a QP for the manufacture of established, licensed products brings significant benefits to an organisation. Examples of this include activities such as active involvement with the continuous improvement of Quality Systems, training, coaching and mentoring. Such activities have delivered greater GMP understanding and awareness resulting in reduced risk of batch rejections or recalls.
Ultimately, the result of this approach to QP input is not only to improve patient safety but also to improve profitability: a true win-win.
Under the Code of Conduct, a QP has a personal and professional duty to keep their knowledge and experience up to date, which covers changes to legislation, GMP standards, pharmaceutical quality management, product manufacturing and general work practices. Early QP involvement in a project gives companies an opportunity to act on current and applicable advice with regards to regulatory compliance.
maximum use of QP skills
In conclusion, the industry needs to be commercially successful, but companies also have an ethical duty to ensure that public safety is paramount at all times. If a company views the QP role as yet another "legal hoop" it has to jump through in order to get a drug to market, it will never get the best from the QP role.
A QP can help companies to ensure that public safety is protected at the same time as helping them cut costs and boost efficiency. In the short term, a QP can cause increased pressure on valuable project resources, but early involvement can result in cost-savings on both current and future projects. QPs are trained to "think what is right" in the drug manufacture process and as such can impart valuable know-ledge on the whole process from development to final release.
In addition to checks on both the processes and products, a QP can use their expertise to mentor staff on a project. QPs can share their knowledge of a number of areas including plant procedures, equipment, analytical methods and manufacturing techniques. This information can be used to develop a QMS that will lay the foundations for all future projects and represents a valuable long-term investment.
