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FDA is working with manufacturers to encourage industry innovation.
Innovation is key to any growing industry, and pharma is no different. Processes in the manufacturing of solid-dosage forms have stayed relatively the same for years. Innovations such as continuous manufacturing, however, have been making strides. In August 2016, FDA stated it was “working with drug makers in a new way to help the industry adopt scientifically sound, novel technologies to produce quality medicines that are consistently safe and effective-with an eye toward avoiding drug shortages” (1). As part of its commitment to fostering innovation, FDA created the Emerging Technology Program (2), which includes the Emerging Technology Team (ETT). The ETT has been working with companies on continuous manufacturing processes such as continuous aseptic spray drying and model-based control strategy. It has also been part of the development of ultra-long-acting oral formulations.
One novel approach that entered the market a couple of years ago was 3-D printing of solid-dosage drugs. It has been said that 3D-printed drugs may be useful for orphan drugs and/or personalized medications that require smaller production lots (3). The first 3D-printed drug approved by FDA in August 2015, however, is produced in commercial scale. Aprecia’s Spritam (levetiracetam) uses a specially developed platform to produce rapidly disintegrating high-dose drugs that are easy to swallow (4, 5).
But has FDA seen more from manufacturers on 3D printing, continuous manufacturing, or other technologies? Pharmaceutical Technology spoke with FDA’s Center for Drug Evaluation and Research (CDER) to catch up on what the agency has been seeing regarding solid-dosage manufacturing.
PharmTech: Since the approval of the first 3D-printed drug in 2015, has FDA developed any further regulations or guidelines for the development of 3D-printed drugs?
CDER: FDA’s Center for Drug Evaluation and Research established an Emerging Technology Team (ETT) to examine and advance applications for new technologies, including 3D printing. What makes this approach novel is that this dialogue can occur during early technology development prior to the submission of a drug application to FDA. Such early engagement enables FDA to proactively identify and address potential roadblocks and helps eliminate potential delay in the adoption of promising new technologies.
FDA issued a draft guidance in December 2015 entitled, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base. While not specific to 3D-printing, the guidance document provides recommendations to pharmaceutical companies on effective ways to work with FDA’s Emerging Technology Team. The document explains the ETT and provides specific recommendations to drug manufacturers for obtaining important early feedback from FDA regarding their efforts to develop novel manufacturing technologies. With respect to 3D printing more generally, in the context of medical devices, FDA issued a draft guidance document in May 2016 entitled, Technical Considerations for Additive Manufactured Devices.
PharmTech: Has the agency seen any problems regarding the manufacture of 3D drugs?
CDER: FDA inspects drug manufacturing to verify that operations are in control and adhere to the approved application methods and control strategy. Drug manufacturing is not without risk and, like other manufacturing operations, must be well-managed and maintained to ensure production and availability of high-quality drugs. FDA collects and evaluates a variety of information about drug quality, and to date we have not seen any noteworthy manufacturing problems with a drug produced by 3D technology.
Drug manufacturing is not without risk and, like other manufacturing operations, must be well-managed and maintained to ensure production and availability of high-quality drugs.
PharmTech: What other new technologies in solid-dosage drug development or manufacture has ETT dealt with?
CDER: The ETT also worked closely with the manufacturer of Prezista, a solid oral-dosage drug for treatment of HIV-1 infection, as they worked on a switch from batch manufacturing to continuous manufacturing technology. The company’s efforts were facilitated by the use of the Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base guidance.
PharmTech: Data integrity has been a hot topic in the past year or so. Are there any other areas FDA is focusing on when inspecting solid-dosage manufacturing facilities?
CDER: Solid oral and semi-solid drugs account for most of the dosage forms consumers take. Thus, facilities that make them still remain the subject of a large percentage of FDA inspections. In addition to attention on data integrity issues, common themes in compliance actions that FDA is observing related to solid-dosage manufacturing include insufficient quality agreements between the sponsor and contract manufacturing organizations, or drug substance manufacturers and quality control labs; and management of the component (active and inactive ingredients) supply chain.
PharmTech: What can you tell us about some of the new and planned guidance documents in regard to solid-dosage products, such as the variety of ANDA guidance documents and Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products; Revised Draft?
CDER: As reflected in CDER’s 2017 Guidance Agenda (6), the agency is diligently working to issue a revised draft guidance on Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products, as well as a number of guidance documents with respect to generics. When the documents are published, stakeholders will have an opportunity to review the guidance documents and provide comments to the dockets. In addition, FDA recently published a draft guidance for comment on Extending Expiration Dates of Doxycycline Tablets and Capsules in Strategic Stockpiles. Other guidance documents listed in the agenda, such as the guidance on drug products that contain nanomaterials, may also include recommendations relevant to solid-dosage products.
1. J. Markarian, Pharm. Tech. 40 (8) (2016).
2. FDA, Emerging Technology Program, accessed June 30, 2017.
3. PharmTech.com, “A Vision for 3D Printing in Pharma Manufacturing,” Sept. 29, 2016,
4. J. Markarian, “Using 3D Printing for Solid-Dosage Drugs,” PharmTech.com, Aug. 17, 2016.
5. PharmTech.com, “FDA Approves First 3D-Printed Drug Product,” PharmTech.com, Aug. 3, 2016.
6. FDA, Guidance Agenda: New & Revised Draft Guidances CDER is Planning to Publish During Calendar Year 2017.
Vol. 41, No. 7
When referring to this article, please cite it as S. Haigney, “Update on 3D-Printed Drugs and What’s Ahead for Solid Dosage Forms,” Pharmaceutical Technology 41 (7) 2017.