E&L and Pharmaceutical Regulatory Compliance AI 

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E&L Problem

WHY DO WE HAVE TO TEST?


🌐 Quality by Design Inc. - Your Trusted Partner in E&L Studies 🌐

At Quality by Design Inc., we pride ourselves on being at the forefront of the Extractables and Leachables (E&L) study landscape. Our comprehensive services cover:


🔍 Consultation on the current E&L study approach 

🔬 Critical assessment and evaluation 

📜 Extractables & Leachables study and profiling 

🧪 Identification & Toxicological evaluations 

🛡️ Risk and Safety assessments 

✅ Regulatory Registration support


Key Areas of Expertise:

  • Container closure systems like glass vials, stoppers, prefilled syringe, patch, medical and related products.
  • Single-use systems and process contact materials such as tubing, bag, filter
  • Steril grade filter related Leachables and Extractables refer to EU GMP Annex 1
  • All types of Medical Devices.

"We proudly showcase our global regulatory expertise, with a track record of obtaining product approvals across:

  • FDA, EMA, CHINA, KOREA, JAPAN, BRASIL, Türkiye(Turkey) and more.

Have an inquiry or need expert advice? 📩 Reach out to us at qbd@qbd.co.kr

For a more in-depth look at what we offer, visit our official website at www.qbd.co.kr

Let's navigate the complexities of E&L together! We look forward to partnering with you. 💼🌟


E&L Study overview


E&L Study 의 목적은 의약품 포장이 안전하고 의약품에 부정적인 영향을 미치지 않는다는 것을 보증하는 것입니다. 이러한 맥락에서 inhaler 와 prefilled syringe 와 같은 의료기기도 1차 포장 시스템 (container closure system) 으로 간주됩니다.


추출물 (Extractables) : 추출물 연구를 위한 추출 시험조건에서, 추출용매로 추출될 수 있는 포장 및 전달시스템, 포장 구성요소(packaging component) 또는 포장 구성 재료(packing materials of construction) 에서 추출되는 유기 또는 무기 화학물질


 침출물 (Leachables) : 일반적인 저장 및 사용조건 또는 가속 안정성 시험 동안 용기 마개 시스템에서 “제형(formulation)” 으로 침출되는 유기 및 무기 화합물


- 침출물(leachables)은 환자에게 바로 투여될 수 있는 유기 또는 무기 화학물질입니다.

Key Referance for DS and DP container closure system


PQRI / USP 1663USP 1664 / ISO 10993 part 1 / ISO 10993 part 12 / ISO 10993 part 18 / ICH Q3E(comming soon, 2025)


Key Referance for Process contact materials for DS manufacturing process and DP manufacturing process 

          USP665 (year 2026) / USP1665 / BPOG /  ISO 10993 part 1 / ISO 10993 part 12 / ISO 10993 part 18


EU GMP Annex 1 : Single use system / Sterile grade filter :: Leachables study 



Other special topic related container closure system

         CCIT (Container closure integrity testing : Dye, Microbial ingress, O2 Head space) / Glass delamination / Silicone oil / Tungsten / Nitrosamine / Teflon / Particulate matter / Elemental impurity.  


 


〈1664〉 ASSESSMENT OF DRUG PRODUCT LEACHABLES ASSOCIATED WITH PHARMACEUTICAL PACKAGING/DELIVERY SYSTEMS


Leachables are foreign organic and inorganic chemical entities that are present in a packaged drug product because they have leached into the packaged drug product from a packaging/delivery system, packaging component, or packaging material of construction under normal conditions of storage and use or during accelerated drug product stability studies. Because leachables are derived from the packaging or delivery system, they are not related to either the drug product itself or its vehicle and ingredients. Leachables are present in a packaged drug product because of the direct action of the drug product on the source of the leachable.


Thus leachables are typically derived from primary and secondary packaging, because the primary and secondary packaging can serve as a barrier between the packaged drug product and other potential sources of foreign chemical entities (e.g., tertiary packaging and ancillary components). In certain circumstances, packaging may directly contact the patient under typical clinical conditions of use (e.g., the mouthpiece of a metered dose inhaler). As a result of this contact, patients may be exposed to leachables from the packaging without the action of the drug product. Leachables are typically a subset of extractables or are derived from extractables. Note that chemical entities can also migrate from packaging/delivery systems to patients via direct contact.  [Lechables와 같은 화학 물질들은 포장/전달 시스템에서 환자로 직접 접촉을 통해 이동할 수 있음.]


부연설명: 

침출물(Leachables)은 drug product의 포장 또는 전달 시스템으로부터 formulation으로 이동하는 다양한 화학 물질을 지칭합니다. 이러한 침출물은 포장 소재나 구성 요소의 화학적 반응으로 인해 formulation으로 이동할 수 있습니다. 침출물은 대부분 포장 또는 전달 시스템의 직접적인 영향 아래에서 발생하며, 이러한 물질들은 사용자나 환자에게 원치 않는 노출을 초래할 수 있습니다. 특히 포장이 환자와 직접 접촉하는 경우에는, 침출물로 인한 노출 위험이 더욱 증가합니다.


USP<1664>의 정의에 따르면, 침출물은 포장 또는 전달 시스템에서 비롯된 것으로, 약제 제품 자체나 그것의 성분과는 관련이 없습니다. 침출물은 약제 제품의 작용으로 포장 또는 전달 시스템에서 약제 제품으로 이동하는 물질들입니다. 따라서, 침출물은 주로 1차 및 2차 포장에서 비롯되며, 이러한 포장들은 약제 제품과 다른 외부 화학 물질들 간의 장벽 역할을 합니다. 그러나 침출물은 포장에서 직접 환자에게 이동할 수도 있습니다.


최근 발생한 recall 사례는 이러한 문제의 심각성을 더욱 강조합니다. Pfizer의 Lipitor, Johnson & Johnson 의 Tylenol 및 Depomed의 Glumetza와 관련된 recall 사례에서, 나무 팔레트에서 발생한 화학 물질인 2,4,6-tribromoanisole이 약물 제품에 침출되어 불쾌한 냄새를 유발한 것으로 밝혀졌습니다. 이 화학 물질은 나무 팔레트에 사용되는 방충제의 부산물로 알려져 있습니다.


TBA는 2,4,6-tribromoanisole의 약자입니다. 이는 나무 팔레트나 포장재에 사용되는 방충제의 부산물에서 발견될 수 있는 화학 물질로서, 때로는 약물 또는 식품 제품에 침출될 수 있습니다. 2,4,6-tribromoanisole은 특정한 양에서 소비될 때 일시적인 위장 질환을 일으킬 수 있습니다. TBA의 오염은 특히 나무 팔레트에서 나오는 냄새 또는 불쾌한 냄새의 주요 원인으로 알려져 있습니다. 


이러한 사례는 침출물이 단순히 포장재에서만 발생하는 것이 아니라, 2차, 3차 또는 4차 포장제에서도 발생할 수 있음을 보여줍니다. 따라서 침출물의 평가와 관리는 약제의 품질과 안전성을 보장하는 데 있어 중요한 고려사항이 되어야 합니다. TBA와 같은 침출물의 위험을 최소화하기 위해서는 적절한 품질 관리 및 테스트 프로토콜이 필요합니다.

“ LeachabLes are a subset of extractables but not all  Leachables are necessarily extractables. “

"침출물(Leachables)은 추출물(Extractables)의 부분집합이지만, 모든 침출물이 꼭 추출물인 것은 아니다."


see also "Migrants"


Genotoxic Impurities Analysis


Pharmaceutical genotoxic impurities analysis services delivered from our GMP labs to support the identification, quantification and control of genotox impurity levels in APIs or drug products to meet regulatory expectations



Genotoxic impurities (GI) analysis is critical to address the purity, safety and quality of drug substances or finished drug products related to potential genotoxic impurities. The ICH M7(R2), a genotoxic impurity guideline defines genotoxicity as “a broad term that refers to any deleterious change in the genetic material regardless of the mechanism by which the change is induced”. There are a range of sources of genotoxic impurities, contributed to reactive materials used in drug substances which have the capacity to interact with human DNA to cause mutations and cancer, even at extremely lowest levels. These substances include a group of potentially high potency mutagenic carcinogens which have “alerting structures” such as N-nitroso-, aflatoxin-like-, and alkyl-azoxy compounds.


Identifying GIs early in the drug development process and/or limiting genotoxic impurities at acceptable levels in the API or drug product, can avoid risks associated with drug safety and quality later in development and/or marketing authorisation, that could potentially lead to expensive recalls. A key example of this are nitrosamine impurities such as N-nitrosodimethylamine (NDMA) which have been highlighted by the US FDA (2018) and other regulatory authorities as an area for concern.


Guidelines from drug regulatory authorities in both Europe and the United States of America (USA) require the control of GIs and potentially genotoxic impurities (PGIs) at parts per million levels in drug substances. Determination of genotoxic impurities at trace levels (lower than 0.01-0.03%) requires highly sensitive and specific analytical approaches that are suitable for the sample matrices of interest and ideally allow detection in the range of 1-to 5ppm.


Our GCP/GLP/GMP compliant laboratories provide genotoxic impurity testing services to detect and evaluate the potential of GIs for your API and/or drug substances which can support your product development from an early stage to market release. With scientists who are adept at method development and validation of suitable analytical procedures, we can overcome the challenges of low detection levels and difficult matrices. Using a range of technologies we can apply an orthogonal approach to ensure robust, specific and sensitive analysis.  Our comprehensive characterisation techniques include: 


  • High Performance Liquid Chromatography with (HPLC with UV/Vis detectors)
  • Gas Chromatography (GC) and GC-MS
  • Liquid Chromatography-Mass Spectrometry (LC-MS)
  • Inductively-Coupled Plasma Optical Emission Spectroscopy
  • (ICP-OES) and Inductively- Coupled Plasma Mass Spectrometry (ICP-MS)
  • Nuclear Magnetic Resonance Spectroscopy (NMR)


As part of our comprehensive stability study capability, we examine degradation products under stressed conditions to help establish degradation pathways. Additionally, we offer highly sensitive and specific method development and validation expertise which is required to address the issues of genotoxic impurities including nitrosamines screening and quantification. 


Toxicological Risk Assessment
With many years of experience in toxicological risk assessments, our consultants conduct risk assessments to address the issues associated with exposure to genotoxic impurities and other substances of concern including residual solvents, process impurities, extractables & leachables, elemental impurities (ICH Q3D) and other substances that may find their way into a pharmaceutical product. 


Total Quality Assurance
Genotoxic impurity testing is one aspect of our global GMP and CMC laboratory services solutions which include pharmaceutical impurity analysis, stability testing, quality control (QC) and batch release testing. Bringing quality and safety to life, we offer Total Quality Assurance expertise to help you to meet and exceed quality, safety and regulatory standards.







Saint-Gobain KOREA Life Science Agency

(주)큐비디

A world leader in the development and integration of innovative materials and components, we create customized single-use solutions for the biopharmaceutical and cell therapy markets. Through our unparalleled technological expertise and worldwide resources, we develop integrated solutions for critical fluid management to meet your evolving needs.

Fluid Transfer

Filtration

Single-Use Assemblies

Containment


Custom design example for overmolding and Single use assembly

- 생고뱅 인천 송도공장 제조 ( ISO Class 7 ) - 




Partner with Quality by Design Inc. (QBD)


Your Gateway to the Korean BioPharma Market

contact@qbd.co.kr

  






At Quality by Design Inc. (QBD), we stand at the forefront of innovation in the BioPharma sector as a distinguished partner for global brands seeking to enter and flourish in the South Korean market. With a decade of excellence, QBD has been pivotal in successfully launching and establishing renowned international services and products in Korea, catering to the dynamic needs of the BioPharma industry.


Our Expertise and Partnerships

Our journey has been marked by robust partnerships with globally acclaimed entities such as Intertek, Artes, Saint-Gobain, and Merck. Through these collaborations, we have specialized in bringing cutting-edge Biopharmaceutical equipment, consumables, raw materials, QC analytical instruments, and more to the Korean BioPharma landscape. Our commitment to quality and innovation has fostered enduring relationships, positioning us as a trusted partner in the industry.


A Call to Future Partners

QBD is actively seeking to expand our portfolio by partnering with brands that aim to penetrate the Korean market with their innovative BioPharma solutions. Whether your offerings encompass CDMO (Contract Development and Manufacturing Organization), CRO (Contract Research Organization), pharmaceutical production technologies, or essential analytical equipment and consumables, QBD is your ideal agency partner in Korea.






Why Partner with QBD?


* Proven Track Record: A decade of successful product and service launches in Korea.

* Strategic Market Entry: Expertise in navigating the Korean BioPharma sector to optimize your market penetration and growth.

* Tailored Partnership Approach: Customized strategies that align with your brand's objectives and the unique aspects of the Korean market.


Let's Explore New Horizons Together

We invite brands looking to make a mark in the Korean BioPharma market to join us in this journey of mutual growth and success. At QBD, we are more than an agency; we are your partner in innovation and market leadership.


For partnership inquiries and to learn more about how we can achieve greatness together, please contact us.


Your success in Korea starts with Quality by Design Inc. (QBD).


contact@qbd.co.kr






제14회 국제의약품·바이오산업전 KOREA PHARM & BIO 2024

2024년 4월23(화) - 26(금) KINTEX 제2 전시장

용기적합성 세미나에 참석해 주시고, 많은 배려 해주심에 안전사고 없이 잘 진행되었습니다.

감사의 말씀 드립니다. 

아울러, 세미나 자료 요청주신 분들이 많아서, 

내부 검토를 통해 제공 가능한 범위의 내용으로 일괄 발송드리고자 합니다. 


E&L 자료가 필요하신분들께서는 아래 메일로 신청해 주세요. 

고맙습니다. 


contact@qbd.co.kr