Michael Sassano: GMP Article No 9: Bringing New Products to GMP Facility

Authored By: Michael Sassano & Antonio Guedelha    Now that your GMP facility has been opened, it’s time to add some new products to your new facility. Luckily, your facility is already GMP-certified, so adding new products is much easier than when you were initially qualifying the facility. Whether it be adding or repurposing rooms,  ordering new equipment and procedures, the process will be smoother with certification.  When it comes to bringing new products to your GMP facility, it’s important to check on the origin. New pharmaceutical products can have origins other than your own research and development (R&D) or may come from other companies that sell application programming interfaces (API) or are interested in product-specific contract manufacturing. Let’s break down the steps for all of these ways to add new products to your facility.  

New Product Basic Data

 In order to begin, you will need an analysis of all the possibilities needed to manufacture the product. The following data is preferred:

• Pharmaceutical approval of the product and main regulatory documentation
• List of raw materials
• List of API’s
• Manufacturing process main steps and main In Process Control (IPC)
• Analytical Methods
• Definition of the packaging materials
• Forecasts
• Documentation requests

GMP Documentation Analysis

Your Quality Assurance (QA) team will receive all documentation, analyze, and distribute the relevant documentation for each department. During the initial analysis, check that the product is indeed a pharmaceutical product by verifying its regulatory approvals. Your pharmaceutical facility cannot produce unapproved pharmaceutical products without special authorization from the proper authorities. During this process, QA will check if the type of product can be manufactured in the facility. Keep in mind, there are some products, for safety reasons and others, that may not be produced in certain facilities. Once approved, your QA will start the procedure of new product analysis, using a document model for new products studies. You will need to draft the new product standard operating procedures (SOP) and change any of your original SOPs that may have changed because of new room usages, new rooms, new equipment, or otherwise. Additionally, the QA will start populating the document with critical information such as necessary supplier audits and a list of all SOPs to be prepared. Ensure the appropriate departments input their information as well. 

Process Equipment Analysis

Process equipment analysis is one of the most critical items to analyze. Begin with an overall analysis to forecast if your manufacturing facility has the proper capacity for product output. If not, you may need to consider more shifts if it is possible. If you cannot add more shifts, rethink the addition of the product line. It may be worthwhile considering a reduction of production size as well. There are other solutions like subcontracting other facilities in part or in whole to do the contract manufacturing. Otherwise, you may need to build a bigger facility to accommodate the volumes. This could be achieved by investing in new rooms or equipment. In any case, the production management team will analyze each step of the manufacturing process to determine if the existing equipment can perform the process step described in the product data. They will promptly verify if the existing machine tools can manufacture the product. IPC compliance tests will be verified to assure the existing testing equipment is adequate. Packaging is critical as there will be checks to guarantee if existing equipment can fulfill product requests and to document which materials and tools are accounted for… The manufacturing team will then estimate the time needed to execute each step of acquisition and expansion. After this analysis is completed, the manufacturing capacity will be checked again. In the case your existing manufacturing facility requires changes, you need to be prepared for the investment. Just as with your original steps when creating new rooms, GMP specifications must be met for any new rooms. When constructing, be sure you are creating minimal dust and mitigating any other possible contaminants. If you are going to create dangers for the existing cleanrooms, you must consider shutting down the operation while you facilitate construction or you might risk contaminating existing rooms and products. Even if you are simply repurposing a room with updated equipment, the process equipment must be ready to operate in the GMP cleanrooms facility. Production Capacity of the equipment must be calculated by determining future sales increases. Depending on the size of equipment, you may need to shut down operations to bring the equipment in or simply through your airlocks while adhering to proper cleaning protocols.   

Laboratory Analytical Equipment Analysis

 Once your team has the proper product data, your Quality Control (QC) laboratory team will verify the needs of equipment, standards, and reactants according to the analytical methods. This requires ensuring the analytical methods used are identified in your region’s Pharmacopeia. In case the pharmacopeia methods exist, it is only necessary to make analytical methods of transfer and validation. If pharmacopeia methods don’t exist (non-pharmacopeia), then you will need to develop analytical methods. Your QC laboratory team will collect all necessary equipment, standards, reactants, analytical methods of transfer, validation, and other documents for the New Products study. Each task will be listed with hours of estimated work till completion.  

Production Cost Calculation

Production costs are also critical. Many companies do not have precise cost calculations nor have implemented the ERP properly with financial forecasting. If the production cost is higher than anticipated and you sign an agreement with a sales price lower than the production cost, it can pose a massive problem for your business. Beware of difficulties that come with the production cost calculation methods you are implementing. Using all the information in the document to new products study, it will be possible to define a Bill of Materials (BOM), with the quantities of raw materials, and a Bill of Activities (BOA), with the time needed for each manufacturing step. You will input this information into the ERP and the production cost will be calculated. Please check and recheck your numbers and methodology.  

Investment Costs

The documents in the New Products study will have all the proper information about investments cost. There are several ways to take your investments into account, but it is critical to get it done. Divide the total value of the investment by your one or more years forecast to arrive at your production cost of the product. Alternatively, assume the investment as a rate of return and use the production cost as calculated to forecast the repayment schedule.  

Quality Assurance Costs

Quality assurance costs will also be calculated based on your new products study. Some of the components will include audit costs, calibrations, validations, reports, and Product Quality Review (PQR). As with the investment calculations, some of this can be divided by the forecast and added to the production costs. These costs are regular for all production, but this must be included in the cost of production to have accurate forecasting.  

Sales Prices Minimum Value and Final Decision

Finally, it’s time to determine your sales price. Based on your production cost, investment cost, quality assurance cost and sales costs, it will be possible to define your sales price, including the sales margin.  With all of the data above, it’s now necessary to verify if the minimum sales price is possible according to the market price. If it’s not and the minimum sales price is high, you may need to redo steps to come in line with the market. You may also need an increase in quantity or look at other ways to decrease production cost enough to meet the market.  This investment must be calculated and verified if the net sales income according to the forecast will allow recovery of the investment, ideally in 2 -3 years. If the product has its origin in your R&D, you need to do this analysis at the start of the R&D process for the product. Avoiding this step is costly if your findings conclude it is not economically possible. This may seem like a lot of effort, but following these steps as you introduce new products into your GMP facility will help you to ensure you make a proper decision for your company’s future.