The Benefits of Designing CDMO Facilities in Anticipation of Annex 1

August 24, 2023

Three reasons Grand River Aseptic Manufacturing (GRAM) is in a positive regulatory position.

In celebration of August 25, 2023, when CDMOs must comply with Annex 1, Grand River Aseptic Manufacturing (“GRAM”) is sharing three ways our facilities, equipment, and team members are prepared to achieve Annex 1 compliance.

  1. Filling and finishing expansions completed in the last three years

In 2018, GRAM broke ground on a new filling facility expansion. In 2020, GRAM embarked on an inspection, filling, and warehouse expansion. At that time, our quality, operations, and engineering leaders already had visibility to Annex 1 requirements and included them in the design of GRAM’s new facilities.

GRAM built material flows, personnel flows, and product flows into their facility designs from the beginning. Personnel enter cleanrooms through dedicated airlocks, while equipment and materials have separate dedicated airlocks. Airlocks used for personnel movement are separated from those used for material movement and are used to minimize microbial and particle contamination. The facilities are outfitted with top-of-the-line utility systems, including an uninterrupted power supply to provide an extra layer of protection for products.

In addition, within the design, GRAM included viewing rooms that allow production visibility from outside our three formulation suites. GRAM’s viewing rooms provide a secure, quiet, and comfortable space for clients, operators, and management to stay for short or extended periods. Each room is equipped with live video feeds of the formulation and filling suites, and inside the filling equipment, giving pathways to view products and providing a safe way to communicate with the team.

 

  1. Equipment with contamination controls and minimal intervention

With recent filling and finishing expansions come innovative equipment and advanced technologies. The latest technologies are focused on minimizing operator intervention and incorporating automation. All four of GRAM’s filling lines and GRAM’s lyophilizer include SKAN isolator technology, which uses glove ports and decontamination cycles within the isolator to eliminate operator intervention. Our commercial scale lyophilizer includes barrier technology with auto-loading and unloading in its separate isolator, making it independent of operator intervention. Before vials reach the fill line they go through a vial washer and then into depyrogenation tunnels, so the containers are sterilized and enclosed through the entire process. GRAM’s fill lines include in-line weight checks and particulate monitoring with notifications and alarms sent directly to the quality, manufacturing, and engineering teams. GRAM’s inspection, finishing, and warehouse center includes four automated inspection systems and eight semi-automated inspection systems that support minimizing operator intervention.

Pre-use post-sterilization integrity testing (PUPSIT) capabilities are present, and a risk assessment is possible to determine whether this testing is necessary. GRAM works with vendors to ensure filters are appropriately added in the right places and performs pre-use and post-use filter integrity tests to show the environment maintained sterile filtration the entire time. Strength in vendor relationships is important and allows GRAM to ensure quality testing can be performed while maintaining sterility.

 

  1. Training with the expectation of Annex 1 requirements

Keeping our team and our client’s drug products safe is imperative. In addition to investing in equipment that supports this, we provide in-depth, recurring training for GRAM employees. Aseptic manufacturing and packaging happen daily, and our team is prepared with the qualifications and experience to protect the drug product’s sterility. GRAM’s quality department oversees environmental monitoring systems that monitor all critical systems, equipment, and controlled spaces at our filling and finishing facilities including alarms, notifications, and reporting of critical data.

GRAM has followed Annex 1 updates for several years and has incorporated the requirements into our procedures. Employees are trained with the expectations of Annex 1 and our on-the-job training, qualifications, and standard operating procedures reflect the requirements.

 

As a leading U.S.-based CDMO, we pride ourselves in our commitment to our team, our customers, and our industry. GRAM has been fortunate to invest in recent facility expansions and innovative equipment that maintains a sterile environment. Our team comprises knowledgeable and experienced sterile fill and finish leaders who joined us from global pharmaceutical companies. Their expertise combined with a culture focused on quality confirms GRAM is prepared now and for the future. GRAM’s preparedness and future-forward vision reinforce the quality services we provide our customers.