Assuring highly potent active ingredient safety: the SafeBridge certification program - Sponsored Whitepaper

Drug innovators, collaborators, licensing partners and the myriad of third parties who handle active pharmaceutical ingredients (APIs) need to take notice when the APIs they are handling have the following properties – clinical doses less than 10 milligrams causing pharmacological or toxic effects in patients or if low doses (less than 1 mg/kg/day) in laboratory animals may potentially be “-genic” (i.e, they are mutagenic, teratogenic, carcinogenic or are reproductive or developmental toxicants). These are the definitions or “red flags” for a “potent” compound which requires containment and controls (“hardware”) and programs and practices (“software”) to minimize worker and environmental exposure. More and more drugs meet these potent compound criteria. Management systems need to be developed by big and small API manufacturing, finished product manufacturing and R&D locations to implement the hardware and software that go beyond traditional approaches to safe handling of “typical” chemicals. Approaches to assuring compliance in pharmaceutical R&D and manufacturing workplaces are typically through audit or assessment of cGMP or GLP compliance. Potent compound safety requires the same degree of assessment as the risks of inadequate containment, lack of exposure controls and improper handling of the API can be significant (for example, causing an adverse health effect in workers handling the drug or impeding speed to market). SafeBridge Consultants, Inc. of Mountain View, California has created and implemented a metric that determines the capability of a pharmaceutical or fine chemical company to meet current industry practices in the health and safety aspects of potent pharmaceutical manufacture and R&D. The process is called the SafeBridge Certification program and it assesses the strengths and weaknesses of the systems, programs and facilities in the area of worker protection. The outcome of the process alerts the manufacturer's management of areas that may not meet current pharmaceutical industry standards or practices. The process utilizes a sixty-point assessment criteria and scoring system developed by SafeBridge health and safety professionals for this purpose. This process can be used as either a “gap assessment” tool for company self-evaluation or as a means to certify, through independent objective review, that the company is

competent in potent compound safety for the purpose of marketing their manufacturing capability to outside parties and potential clients. Specific regulations for occupational exposure prevention to highly potent pharmaceutical materials do not exist and the industry is largely self-regulated regarding pharmaceutical product exposure control. Common approaches have been developed by the large pharmaceutical companies to meet their ethical obligations and the “general duty” regulations of providing a safe and healthful working environment. Therefore the Certification process is not a strict regulatory audit, rather the assessment is designed to determine the gaps that companies seeking contract pharmaceutical product development and clinical and commercial manufacturing could identify when evaluating the capabilities of a company in potent compound safety.

The process involves a pre-visit questionnaire issued to the company regarding the nature of the facility, processes and programs in environmental health and safety (EH&S) that may affect manufacturing. The company will provide SafeBridge with responses to the pre-visit questionnaire and, if available, the following information: · Engineering design drawings of the layout of the facility; · An equipment inventory; ·Achemical inventory or, at a minimum, a list of active pharmaceutical ingredients (APIs) used at the facility; · Any descriptions of existing exposure control technology; ·Process flow diagrams for each typical process employed; · Control Matrix (or control banding system); and · Relevant Standard Operating procedures (SOPs).

SafeBridge Certification in potent compound safety is based on the successful implementation of the “systematic approach” to potent compound safety (see sidebar). The on-site assessment includes evaluation of both physical plant and equipment items (such as air pressure

14 chimica oggi · Chemistry Today · May 2004