Q&A: Long-Acting Implants: Design for Durable Drug Delivery

Seth Forster, Merck

Q: Is the implant removable in between time?
A: The implant may be removable during or at the end of therapy. Most currently available biodegradable polymers (PLGA, PLA) degrade throughout the implant over time, so it may be challenging to remove partway through its use. Surface eroding biodegradable polymers retain more mechanical strength over time. Biodurable polymers (EVA, TPU, Silicones) will usually retain mechanical integrity in vivo and can be removed after therapy. 

Q: Can implant be manufactured aseptically using the extrusion process?
A: Implants must be made with low bioburden and endotoxin levels, usually in a cleanroom environment to avoid particulate or biological contamination. If the product is not stable when irradiated for terminal sterilization, it may be feasible to sterilize the product contact parts of an extruder, depending on the equipment’s design, and process in an aseptic environment.

Q: Can you describe the in vitro release assay shown on slide 13?
A: The in vitro release study was using an automated flask shaker incubator with a fixed volume of phosphate buffer saline (PBS). Automated flow-through dissolution and sampling systems like the USP Apparatus 7 can also be used.

Q: How much material do you need for your early investigations when you choose a suitable carrier?
A: Pilot scale extrusion batches require 250 – 500 g of total formulation, but some small scale twin-screw extruders can process with as little 5 – 10 g of formulation.
We continue to work to reduce the amount of API for prototyping. Injection molding and vacuum compression molding techniques can make prototypes for initial testing, but we do not know yet if these will predict performance at scale.

Q: What equipment do you use to cut filaments in the laboratory scale and in the larger manufacturing scale? How reproducible is the process?
A: At the smallest scale, we use a razor blade to cut while a small fixture holds the implant. Fragile rods can be placed in tubing to hold them square for cutting. At larger scale, filaments can be cut using off-line and on-line cutting equipment used for medical tubing

Q: Has the implant mfg process been used for biologics API?
A: Extrusion exposes APIs to high temperatures and high shear. Some peptides and biologics can tolerate this process, especially when isolated as solids. 

Q: For a non-degradable implant, where release is maybe more dependent on a completely connected API network, what is the minimum API loading that is often needed (if there is a minimum)? And how does this depend on the hydrophobicity of the API?
A: In our experience, a non-degradable matrix implant does have a minimum filler loading to establish a complete pore network, roughly 30%w/w. The minimum level is a function of filler size and morphology. The expected volume fraction can be estimated by percolation theory. Note that the “fillers” could be API or API and other excipients.
The loading level required for complete release does not seem to be related to hydrophobicity of the API, though there may be reduction in the release rate related to the API’s affinity for the polymer or if the API dissolves into the polymer and cannot dissolve out when exposed to fluid.

Q: How is the cutting process made? 
A: Refer to response #5.

Q: How is the microstructure of the implant determined and what parameters are used to assess the reproducibility of these microstructures?
A: We have used several imaging tools to characterize the implant microstructure. X-ray computed tomography (XRCT) has been especially helpful.
For more information: Skomski, Daniel, et al. “An Imaging Toolkit for Physical Characterization of Long-Acting Pharmaceutical Implants.” Journal of Pharmaceutical Sciences (2020).

Q: What are some of the API characteristics that would make a long acting implant delivery not a feasible strategy? Would a short half life impact this decision?
A: For a long acting implant to be feasible, the API input rate per day should be roughly 1 mg/d or less. Input rate = Ctrough x Clearance, so it is related to the potency and the clearance of the API. A short half-life, i.e. rapid clearance, means a higher input rate and more difficulty in development.

Q: Which is the better option regarding lubricants
A: Lubricants as process aides should be compatible with the formulation and biocompatible for the duration of use. Compare with other parenteral products and implantable medical devices for examples.

Q: What is the usual preclinical safety/toxicology studies usually required for long-term (> 6 months?) implants?
A: Refer to ISO 10993, Biological Evaluation Of Medical Devices for testing requirements,    depending on location and duration of use. In general, an in-life toxicology test is likely to be      required in addition to local irritation and in vitro safety tests.

Q: What is the best method for terminal sterilization of biodegradable products?
A: The preferred terminal sterilization method is highly dependent on the API and formulation. For long-acting implants, gamma irradiation is probably most often used, though other types of irradiation like e-beam or X-ray may be more compatible with biologics. The dose of irradiation is another important consideration: typically 25 – 40 kGy is used as a default, but lower doses may be justified if necessary to protect the stability of the product.

Q: Would it be great to have In-Situ forming implants compared to solid implants? Can you share a little bit on how in situ forming implants field is growing or not at all?
A: In situ forming implants are attractive, particularly if they are patient administered and biodegradable. Commercial examples are Sublocade (buprenorphine q1m) and Perseris (risperidone q1m), both using PLGA. In situ implants tend to be more porous and higher surface area so they may be more challenging to achieve drug releases beyond a month or two. 

Q: What kind dissolution media is used on slide 11 for in vitro release? And what kind of dissolution apparatus?
A: The in vitro release study shown on this slide was performed in flasks containing phosphate buffer saline (PBS) continuously gently agitated in an incubator shaker at 37°C. Alternatively, USP IV or VII apparatus can be used.

Q: How do you generate first prototypes when you work with NCE with limited availability?
A: We have used small-scale extrusion and molding to make prototypes with 1 – 10 g of API. There is more work to be done to scale this down further and confirm scalability to pilot and commercial scale.

Q: When the duration is long like 3 to 5 years, can the drug release rate decrease due to the growth of fibrous tissues around the implant?
A: Yes, this is described in the literature and occurs as rapidly as a few weeks after implantation. This phenomenon highlights the importance of in vivo testing.

Q: Most of the biodegradable polymeric implants change release profile after sterilization. Any comments?
A: Both biodegradable and biodurable polymeric implants can change drug release profile after sterilization and as a function of radiation dose. It is important to assess the impact of irradiation during development.

Q: Can you please name of all instruments required for formulation and characterization of implants?
A: This depends on many factors. The process described in the talk to make implants uses mills, twin-screw extruders, sieves, single-screw extruders, automated cutting equipment, visual inspection equipment, and device assembly equipment. Characterization involved typical wet chemistry testing, solid state characterization, and, because of the long duration of testing, specialized drug release testing equipment. 

Q: Could you please explain API physical and pharmacological properties?
A: The API’s physicochemical and pharmacological properties can impact the formulation approach in many ways. The ideal molecule would have a low dose and slow clearance. It would be chemically and physically compatible with heat, shear, and the formulation components.

Q: How do you screen for matrix + skin systems?
A: We have used a few approaches, including producing coextruded implant prototypes at pilot scale, filling core material into tubes, or layering between films of the rate-controlling membranes. These have had varying degrees of success in predicting performance of implants made at commercial scale.

Q: How does high drug loading affect in vitro release behavior of PLGA microspheres?
A: I am not an expert in this area. However, there are several literature examples of drug loading limitations for PLGA microspheres, similar to matrix implants. As the drug loading increases past a certain point, generally 10 – 30%w/w, it becomes more challenging to control the release rate with the excipients, and it is dominated by the API properties.

Q: Can you share more on how reservoir type implants manufactured and what are specific controls related to that? Any thought on implants for biologics ?
A: Reservoir systems require an integral, consistent coating without bubbles or gaps. For coextruded products, the position of the core and coating thickness can vary in an individual implant and across the batch and impact the drug release.
Biologic APIs are challenging to formulate using typical processing, though isolation as a solid with stabilizing excipients can help improve the thermal and shear processing. Gentler, lower temperature approaches are needed to effectively deliver biologic APIs over a long period.

Q: What can be the effective strategy for formulating hydrophilic drug implant?
A: Provided it is sufficiently potent, a hydrophilic API can still be formulated as a long-acting implant. For a hydrophilic API vs a hydrophobic one, the drug release is likely to be more sensitive to the drug loading and the water permeability through the matrix or rate-controlling membrane.

Q: Are there specific models of IVIVC (in vitro – in vivo correlation) that you refer to for long-acting implants?
A: An IVIVC can sometimes be made for long-acting implants based on empirical data but, unfortunately, it is difficult to predict a priori what the correlation will be.

Q: Are there differences in ease of terminal sterilization between the degradable and non-degradable implant systems?
A: Terminal sterilization, depending on type and dose, can impact drug release from biodegradable or biodurable formulations. 

Q: How many generic implantable products are on the market?
A: I am not aware of any approved generic long-acting implant products. Several products are novel delivery systems for generic APIs.

Q: What are challenges in matching release profiles developing generic products?
A: Generic long-acting injectible formulation development is challenging. Over the last few years, the US FDA has invested resources to improve technical understanding (reference 1, 2) and build predictive tools for generic development.

Q: What challenges are experienced regarding stability of API in the implants (a) before implantation and (b) once implanted? Is there a risk of degradation or other stability issues with the API molecule under various conditions and lengths of time?
A: The API should be (a) stable in the formulation, in the primary packaging that is selected, before and after irradiation and (b) stable in the subcutaneous space for an extended period of time. Some APIs will degrade at body temperature and may not be suitable for long-acting implants.

Q: What tests are used to determine if an implant is stiff enough to administer but won’t break/bend during use? Is there a range of Young’s modulus that will inform this?
A: Tensile strength and three-point bending testing can help inform the risk of discomfort, breakage, or bending, though more work is required to predict the clinical impact from these tests.

Q: Is there any requirement to generate stability data and do we have to prove bioavailability?
A: Stability data and in vivo drug release data would be required.

David Preston
David Preston


David Preston has had 38 years of healthcare experience with publicky Traded and Private companies in the fields of Phammaceuticals, Animal Health and Biotechnology as a Board Member. The last 30 years of his xperience has been in China, Taiwan and Hong Kong building successful igh growth businesses. David Has been Chaiman and CEO for Greater China for Sanofi and Boehringer – Ingelheim as well as the Janssen Corporation since 1991 in China. During this time he build high Growth ousinesses in China through diversified strategies in Innovative Pharmaceuticals. branded Generics. Biotechnology. and Animal Healthcare.

Key highlights in this period indluded building of the first Westem Multinational Biotechnoloqy C.M.O. facility as well as obtaining the first Test CM.OJ MAHI license. Establishment of a number of High tech Vaccine Plants, and R and D facilities in in the field of Animal Health. Signing and development of numerous JV’s as well as Wholly owned Subsidiaries. Mergers and Acquisitions across Phamaceutical’s. Animal Health. and Biotechnology industries

David’s achievement’s in the Healthcare industry and it Growth and development in China is widely recognized By the Chinese Govemnment and the City of Shanghai In 2013 he was awarded the Silver Magnolia ollowed in 2015 the Gold Magnolia award. This was then followed by being awarded in 2017 the Honorary Citizen of Shanghai by 40th People’s Municipal Congress of Shanghai. David Holds a Business Science Degree

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Filippo de Vecchi

Director, Advent Partner

Filippo de Vecchi joined Advent in February 2000. He started in the Advent São Paulo office, then moved to Milan in 2002, in 2012 set up the Advent office in Shanghai and in 2016 set up the Hong Kong office. Before joining Advent, he was a senior consultant with Value Partners, in São Paulo and Milan, focusing on strategy and organization in the automotive, energy, cable and media sectors. He began his career at Wasserstein Perella & Co., working as an analyst in the Mergers and Acquisitions department in London and New York. Filippo holds an undergraduate degree cum laude in Economics, with a major in Business Administration, from the LUISS University and an MBA from Columbia Business School, where he currently serves as a member of the Board of Overseers.

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Andrew Li
Andrew Li

Director, Advent Partner

Andrew Li joined Advent in 2012. He previously worked at Warburg Pincus, HSBC PE, Solera Capital and Credit Suisse where he focused on the retail and consumer, healthcare, industrial, and energy sectors. Andrew has worked in finance and private equity throughout the U.S. and China since 1999. Andrew holds a BA from Middlebury College and an MBA from Harvard Business School.    

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Michael Miltenberger
Michael Miltenberger

Director, Advent Partner

Michael Miltenberger  joined Advent in 2011 as an associate on the healthcare team. Following business school, he rejoined Advent’s Boston office, focusing on healthcare investments. Prior to Advent, Michael was a consultant at McKinsey & Company in their Washington DC office, serving a range of healthcare and private equity clients. Michael earned a BA, cum laude, from Harvard College and an MBA from Harvard Business School, graduating with High Distinction as a Baker Scholar and a Harvey Fellow.

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Masood Tayebi
Masood Tayebi, PhD

Director, Operating Partner

Dr. Masood Tayebi is the Founder of BioDuro. He currently serves as CEO of a nationwide real estate portfolio and is a Partner and Chief Executive Officer of the Bridgewest Group. Prior to BioDuro, Dr. Tayebi was Co-Founder and Chairman of Wireless Facilities, Inc. (NASDAQ: WFI), a global leader in telecommunications outsourcing.

  • Co-Founder of Wireless Facilities, Inc.

  • Co-Founder of BioAtla, LLC

  • Recipient of the Ernst and Young 2000 Entrepreneur of the Year award in San Diego

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Kewen Jin
Kewen Jin, PhD

Director, Operating Partner

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Amit patel
Amit Patel

Director, Operating Partner

Amit Patel has twenty years of healthcare industry experience with publicly-traded, private equity-backed, and start-up companies in the capacity of executive, board member, advisor, and investor.  He is currently Executive Chairman of Azurity Pharmaceuticals (a NovaQuest Capital Management portfolio company) and a board member at BioDuro (Advent International portfolio company), Tergus Pharma (Great Point Partners portfolio company) and Calyptus Pharma.  Recently, Amit was SVP & President of Dosage Form Solutions at Capsugel, a KKR portfolio company (purchased from Pfizer in 2011 and sold to Lonza in 2017).   

Prior to Capsugel, he worked at Dr. Reddy’s Laboratories, Inc. as EVP & Head of North America, and SVP & Head of Global Corporate Development & Strategic Planning. Earlier, Amit was VP of Corporate Development at CTIS, Inc., and Co-founder & CEO of MedOnTime, Inc. (acquired by CTIS).  He started his career as a strategy consultant with Marakon Associates. Amit holds an M.B.A. degree from Harvard Business School, a B.S. degree in Economics from the Wharton School of Business, University of Pennsylvania, and a B.A.S. degree in Systems Engineering from the Moore School of Engineering, University of Pennsylvania.

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Haijun Dong
Haijun Dong

Chief Executive Officer

Dr. Haijun Dong currently serves as global CEO of BioDuro-Sundia. He previously was CEO for over 5 years at PharmaBlock Sciences Inc., a public company listed in the Shenzhen Stock Exchange (300725.SZ). The positions he held prior to PharmaBlock includes, among others, Senior Scientist at Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut; Senior Principal Scientist at Roche in Nutley, New Jersey; Head of DMPK and Drug Safety at Roche China R&D Company in Shanghai; Chief Operating Officer of Eli Lilly China R&D Center in Shanghai.

Dr. Dong received his PhD in organic chemistry from the University of Washington in Seattle, Washington, and MBA from China Europe International Business School in Shanghai. 

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Teo Nee Chuan
Teo Nee Chuan

Chief Financial Officer

Teo Nee Chuan joined us in May 2021 as chief financial officer. Prior to joining us, he was chief financial officer of Huazhu Group from November 2015 to May 2021, and was the chief financial officer for Rnomac International Limited, from November 2011 to August 2015. Mr. Teo worked in DDB Greater China Group, was appointed as the chief financial officer in September 2009, and was additionally appointed as the director of operations in January 2011. He previously served in Focus Media Group and was appointed as the financial deputy director in June 2007. Prior to that, from September 1994 to May 2007, Mr. Teo worked at Ernst & Young and Ernst & Young Business Services Ltd. in various positions in Kuala Lumpur and Toronto, including as a senior manager in the Transaction Advisory Services. Mr. Teo has been an independent director of 111, Inc. (a company listed on the NASDAQ, ticker symbol: YI) since September 2018. Mr. Teo received his Bachelor of Science in Accounting and Financial Analysis degree from The University of Warwick in the United Kingdom in July 1994. He is a Chartered Certified Accountant in the United Kingdom, who has obtained his qualification in July 1998 from The Association of Chartered Certified Accountants, and is a Certified Public Accountant in the United States and Hong Kong, who has obtained his qualification from American Institute of Certified Public Accountants in May 2002 and Hong Kong Society of Accountants in October 2003, respectively.

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TJ Deng, PhD

President, Discovery

Dr TJ Deng joined BioDuro in the initial stages of the company and helped BioDuro grow to an industry leading discovery services organization. He established and managed several scientific departments, including DMPK, before transitioning to a leader of the business and operations functions. Prior to joining BioDuro, Dr. Deng spent six years at PPD, in positions with increasing responsibilities from scientist to scientific manager.




  • Developed the extractable/leachable capabilities at PPD
  • 18 years industry experience

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Kent Payne
Kent M. Payne, PhD

Chief Executive Officer

Kent is distinguished as a business operator and leader in areas of sales, commercial manufacturing and product development. He has extensive executive experience in M&A as well as successfully running, start up, growth and turn around businesses. This includes both Fortune 500 and Private Equity environments. He combines strong business leadership, successful P&L track record, and technical background to strategically lead and grow enterprise value across Biotechnology and Pharmaceutical market segments. He has successfully led the geographic expansion of businesses into Europe, Asia, and South America in addition to the United States.  He currently serves as CEO for BioDuro-Sundia, LLC (an Advent International company). He also currently serves as a board member for Goodwin Biotechnologies (a Signet Healthcare company). 

Prior Roles

  • President, Global CMC Solutions BioDuro-Sundia, a global
  • CEO Socorro Pharmaceuticals, LLC, a generic pharmaceutical
  • President Americas, Qualicaps Inc.(a Mitsubishi Chemical Holdings subsidiary)
  • Principal Consultant and Partner at CoreFactor LLC, providing executive strategic, licensing and operational advisory services to clients.
  • Vice President/General Manager Catalent Pharma Solutions, Inc. (a Blackstone Group company formed in 2007, formerly part of Cardinal Health)
  • Progressive leadership responsibility at: Novartis, Monsanto and G.D. Searle.  

Prior Brand Position

  • Board Advisor Vitruvias Therapeutics
  • Board Member Qualicaps, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board member Technophar, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board Advisor, Corporate Strategy Office, Life Science Institute
    Inc. (a wholly owned subsidiary of Mitsubishi Chemical Holdings)
  • Non-executive Chair and Board Member PDS Biotechnology·        (PDSB: NASDAQ)

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John Phillips
John Phillips

Vice President, Business Development (US & EU)

Coming soon…



  • Coming soon…

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Roy Xu
Roy Xu

Chief Strategy Officer

Roy has over 25 years of healthcare industry experience.  He started his career as an orthopedic surgeon.  Roy joined Eli Lilly as a sales rep in 1997.  Since then he has had various roles in market research, business intelligence, BU head, strategy, regional general management, business development etc., both at Eli Lilly and Boehringer Ingelheim (BI).  Roy also spent more than two years in Germany where he was BI’s Director of Corporate Business and Enabling Strategy.

Roy obtained a bachelor’s degree in Clinical Medicine at Zhejiang Traditional Chinese Medicine University, and an MBA from Zhejiang University.



  • 25 years of healthcare industry experience including Eli Lily and Boehringer Ingelheim. 
  • Former Director of Corporate Business & Enabling Strategy at oehringer Ingelheim in Germany.

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San Diego

San Diego - BioDuro-Sundia

Our San Diego site is our corporate headquarters. The facility is home to BioDuro-Sundia’s drug product development technologies and has 9 GMP clean rooms. Development and manufacturing operations are conducted for projects up to Phase III clinical trials.

Size: 44,000 sq. ft.
Featured capabilites: Tableting, Coating, Hot Melt Extrusion, Spray Dried Dispersion

11011 Torreyana Rd.
San Diego
CA 92121
United States

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BioDuro Beijing

Operating since 2006, our Beijing site is home to BioDuro-Sundia’s first wet chemistry operations. With 300 regular fume hoods and 18 scale-up chemistry hoods the Beijing facility houses most of BioDuro’s chemistry operations, while also hosting labs for biology and monoclonal antibody discovery.

Size: 100,000 sq. ft. 
Featured capabilities: Radioactivity Lab, Monoclonal Antibody Discovery, Medicinal Chemistry

No. 29 Life Science Park Road
Changping District Beijing,
P.R. China

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BioDuro- Shanghai Facility

Established in 2012, BioDuro-Sundia’s Shanghai facility has been growing with its departments. The cutting edge facility contains labs for ADME, bioanalysis, in vitro assays and translational research. The site includes a 18,000 sq. ft vivarium and 20,000 sq. ft of office space.

Size: 92,000 sq. ft.
Featured capabilities: Scale-up Chemistry, Discovery Biology, DMPK, In Vivo Pharmacology

No. 233 North Fu Te Road
Waigaoqiao Free Trade Zone
Shanghai, 200131
P.R. China

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Cathy Yen
Cathy Yen

Director, Operating Partner

Cathy joined the Board of Directors of BioDuro-Sundia in 2020, with the Advent-led acquisition of Sundia and creation of BioDuro-Sundia. Prior to that, she was Chairman of the Board at Sundia Meditech Group, where she was the key architect of Sundia’s strategic vision and growth. Under her leadership, Sundia solidified its position as one of the leading pre-clinical CROs in China.

Prior to Sundia, Cathy had a distinguished career as a seasoned venture capitalist, having led numerous investments in high-growth companies in Asia. Cathy served as a Partner of AsiaVest Partners, TCW/YFY Ltd., a global venture capital firm, for over a decade, Vice President at Global Financial Services, Vice President at Crimson Ventures/Chinatrust Bank and Senior Manager at Fortune Capital. She brings over 20 years of experience in corporate finance, accounting, strategic planning and private equity investments. 

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Wuxi - BioDuro

Established in 2019, BioDuro-Sundia’s fully integrated discovery facility located at the heart of Jiangsu Wuxi Life Science & Technology Industrial Park with plans of growing staff to 1000+ scientists.

Size: 300,000 sq. ft.
Featured capabilities:
Discovery Chemistry & Biologics, Biology, DMPK, Pharmacology, CMC Services

no.1699,Huishan avenue
Huishan Economic 
Development Zone,Wuxi
P.R. China

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Hebei - Sundia

Established in 2011, this pilot plant this handles mg to kg scale up.

Size: 45,208 sq. ft.

Featured capabilities: SFFS Chemistry: mg to kg scale up
(150 hood)

238 Changjiang Road
Hebei province
P.R. China

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