We are subject to significant regulatory oversight with respect to manufacturing our product candidates. Our manufacturing facility may not meet regulatory requirements.
The preparation of therapeutics for clinical trials or commercial sale is subject to extensive regulation. Components of a finished therapeutic product approved for commercial sale or used in late‑stage clinical trials must be manufactured in accordance with cGMP requirements. These regulations govern manufacturing processes and procedures, including record keeping, and the implementation and operation of quality systems to control and assure the quality of investigational products and products approved for sale. Poor control of production processes can lead to the introduction of outside agents or other contaminants, or to inadvertent changes in the properties or stability of a product candidate that may not be detectable in final product testing. We must supply all necessary documentation in support of a BLA or other marketing authorization application on a timely basis and must adhere to the FDA’s and the European Union’s cGMP requirements which are enforced, in the case of the FDA, through its facilities inspection program. Our manufacturing facilities and quality systems and, to the extent that we utilize third‑party facilities for commercial supply, the third party’s facilities and quality systems, must pass an inspection for compliance with the applicable regulations as a condition of regulatory approval. In addition, the regulatory authorities may, at any time, audit or inspect the third‑party manufacturing facility or the associated quality systems for compliance with the regulations applicable to the activities being conducted. If these facilities do not pass a plant inspection, the EMA will not issue a positive opinion concerning the marketing authorization application and FDA approval of the product candidates will not be granted.
If any contract manufacturers that we engage in the future cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or foreign regulatory agencies, they will not be able to secure and/or maintain regulatory approval for their manufacturing facilities. In addition, we will have no direct control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. Furthermore, all of our contract manufacturers are engaged with other companies to supply and/or manufacture materials or products for such companies, which exposes our manufacturers to regulatory risks for the production of such materials and products. As a result, failure to meet the regulatory requirements for the production of those materials and products may generally affect the regulatory clearance of our contract manufacturers’ facility. Our failure, or the failure of our third parties, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products and product candidates.
Our potential future dependence upon others for the manufacture of our product candidates may adversely affect our future profit margins and our ability to commercialize any products that receive regulatory approval on a timely and competitive basis.
Risks related to the commercialization of AVXS‑101
Gene therapies are novel, complex and difficult to manufacture. We have limited manufacturing experience and could experience production problems that result in delays in our development or commercialization programs or otherwise adversely affect our business.
We have limited experience manufacturing AVXS‑101. Although we have established our own manufacturing facility to support current and future clinical trials and a commercial launch, if we are unable to receive regulatory approval for our facility, we may be unable to produce clinical or commercial materials or meet demand, for AVXS‑101. Any such failure could delay or prevent our development of AVXS‑101 and would have a material adverse effect on our business, financial condition and results of operations.
The manufacturing process we use to produce AVXS‑101 is complex, novel and has not been validated for commercial use. In order to produce sufficient quantities of AVXS‑101 for future clinical trials and initial U.S. commercial demand, we will need to increase the scale of our manufacturing process at third‑party manufacturers, as well as through continued investment into our own commercial scale manufacturing facility. We may need to change our current manufacturing process, but there are no assurances that we will be able to produce sufficient quantities of AVXS‑101, due to several factors, including equipment malfunctions, facility contamination, technical process