What kind of permits and certification do young biotech companies need? Do particular requirements in the quality assurance of production processes based on initial permits still have to be taken into account 10 years after foundation? Ten years on, it may in fact be necessary to obtain different certificates that take external factors into account as well as changes in a company’s product and service portfolio. But what do ISO 9001, ISO 13485, GLP or GMP mean? We gained further insights into quality management from two Freiburg-based companies – Diarect AG and M-Scan GmbH.
People wishing to set up a biotech company need to take a number of things into account. Company founders must register their enterprise in the commercial register in the same way as a bakery or a shoe shop. Biotech companies also have to obtain a laboratory permit from a government safety organisation. If a company plans to work with genetically modified organisms (GMOs), authorisation needs to be obtained from the respective state authorities. “These are the basic requirements,” said Dr. Heinz Haubruck, CEO of Diarect AG in Freiburg. “The next steps then depend on the particular product a company intends to produce.”
Diarect AG offers its clients, which are mostly from the medical field, high-quality immunodiagnostics components, including antigens, i.e. proteins or nucleoproteins that induce an immunological reaction and that can be used for antibody tests. These molecules have to conform to the highest purity standards. There must be no contamination of the solutions by unwanted, foreign antigens, as this would falsify the antibody tests. The activities of the substances must remain unchanged over a period of many years. Specific strict quality management processes have to be put in place to control production, enrichment, purification, storage or transport processes.
There are several different quality management systems a company can establish in order to guarantee high product quality. The processes at Diarect AG are certified according to the internationally recognised ISO 9001 standard. The company received an ISO 9001 certificate in 2002 following an inspection by the DQS GmbH Deutsche Gesellschaft zur Zertifizierung von Managementsystemen. This certificate was renewed in 2008 and is valid until 2011. The company also obtained a DIN EN ISO 13485 certificate in 2008. "The ISO 9001 certificate is important for all companies, no matter what product or service they provide," said Dr. Armin Neininger, Head of the Department of Quality Assurance and Quality Control at Diarect AG. "This certificate attests that all general production processes are adjusted to each other in an optimal way and undergo constant improvements." Certification also involves regular staff training, documentation and constant control of individual process steps.
The 13485 certificate is more demanding. It is specifically designed for manufacturers of medical products. “In order to obtain such a certificate, medical device manufacturers have to show that their production process is in conformance with valid medical standards,” said Neininger. For example, the production of antigens requires controls to be carried out after each production step. The final product is then characterised using biochemical, immunochemical and other specific analyses. All steps, from purchase of the raw materials to production, storage and delivery to clients, must be documented and controlled. The laboratories and devices have to undergo regular maintenance and specialist staff training is obligatory. Internal and external inspections by experts from DQS GmbH are carried out every year.
The requirements are a lot higher for companies that are active in the drug sector. Freiburg-based M-Scan GmbH is an independent laboratory that analyses the chemical structure of newly developed potential active drug ingredients. It also checks these substances for potential contaminations. The active substances include complex biopharmaceuticals such as proteins, antibodies, nucleotides or sugars as well as smaller chemical molecules. In addition, M-Scan also develops analytical methods for its clients, which can be used for the continuous quality control of new drug charges. The activities of M-Scan require the company to put in place different quality management systems, depending on the development process of a drug substance.
"If the substance is still in the preclinical test phase, companies such as M-Scan require a Good Laboratory Practice, or GLP, certificate," said Dr. Matthias Berg, Head of Laboratory at M-Scan. This certificate, which is designed to prevent laboratory data from being falsified, documents that the analyses have been carried out according to strict quality criteria. M-Scan GmbH expects to receive its certificate within the next few days; the company and its processes have just passed an inspection by the Baden-Württemberg government.
At the end of 2008, the Freiburg-based company had already obtained another certificate that certifies that it works according to the criteria of what is known as Good Manufacturing Practice (GMP). GMP is a term that is recognised worldwide and that attests the quality control testing of active drug ingredients, pharmaceutical products and medical devices. “A GMP certificate is important for our clients when their potential drug enters clinical testing and is tested on patients. “But it also entitles us to carry out release analyses on any new package of already approved drugs that enters the pharmacy.” Guaranteed quality is of central importance in the production of drugs; GMP is therefore designed to help ensure the quality of drug products intended for human application. The GMP certificate certifies that analyses are carried out according to the quality standards of German and international drug authorities (BfArM, EMEA, FDA etc).It is not easy to obtain certification of any kind, whether it be ISO 9001, DIN EN ISO 13485, GLP or GMP certificates. “A company’s entire manufacturing process must follow strict criteria,” said Berg. Of course, it is also possible for biotech companies to gain an initial foothold without having such quality management measures in place. But a growing number of clients require the quality of products and services offered to be specifically certified. It is advisable to set up a quality management system as soon as possible after establishment. “If a company leaves the implementation of a system like this until a few years after its foundation it runs the risk of slowing down the process, which could have an effect on overall success,” said Prof. Dr. Bodo Liedvogel, CEO of Diarect AG. “Implementing a quality system at a late stage not only costs a lot of money, but also requires a lot of time, which would be better spent acquiring new clients and orders.” Late implementation of a quality system might prove to be a considerable drawback, and even cause a company to go out of business in this very dynamic market.mn
Further information: Dr. Armin NeiningerHead of Quality Assurance and Quality Control DIARECT AGBötzinger Strasse 29 B79111 FreiburgTel.: + 49-(0)761/47 979-0Fax: + 49-(0)761/47 979-29E-mail: armin.neininger(at)diarect.comDr. Matthias Berg Head of LaboratoryM-Scan GmbHBioTechPark FreiburgEngesserstr. 4a79108 Freiburg i.Br.Tel.: +49-(0)761/611 677-60Fax: +49-(0)761/611 677-66E-mail: services.de(at)m-scan.com